{"meta":{"title":"GLP-1 and peptide molecule facts","description":"Core facts for each molecule: class, targets, plain and expert summaries, evidence level with its sources, route, half-life and key facts. Every value carries its source.","publisher":"GLP1 Base","url":"https://glp1base.com/data","license":"https://creativecommons.org/licenses/by/4.0/","licenseName":"Creative Commons Attribution 4.0 International (CC BY 4.0)","attribution":"GLP1 Base (https://glp1base.com), powered by KeenShift. Licensed CC-BY-4.0.","howToCite":"GLP1 Base (2026). GLP-1 and peptide regulatory status by country [dataset]. KeenShift. https://glp1base.com/data (accessed YYYY-MM-DD). CC-BY-4.0.","dateModified":"2026-09-29","disclaimer":"Educational information only. Not medical advice, not a recommendation to use any substance, and not an offer to supply. Talk to a licensed clinician about your own care.","contact":"mitsi@keenshift.ai","count":36,"evidenceLevels":{"approved":{"label":"Approved","meaning":"Approved by a major regulator after large trials."},"phase3":{"label":"Phase 3 trials","meaning":"Large trials comparing it with placebo or other drugs."},"phase2":{"label":"Phase 2 trials","meaning":"Mid-size trials testing if it works."},"phase1":{"label":"Phase 1 trials","meaning":"Early safety trials in people."},"human-small":{"label":"Small human studies","meaning":"Small or uncontrolled studies in people."},"animal":{"label":"Animal studies only","meaning":"Tested in animals, not properly in people."},"cell":{"label":"Cell studies only","meaning":"Only tested on cells in a dish."},"anecdote":{"label":"Anecdote only","meaning":"Only personal stories or forum reports."}}},"molecules":[{"slug":"amycretin","name":"Amycretin","url":"https://glp1base.com/molecules/amycretin","aliases":["Zenagamtide","NNC0487-0111"],"brands":[],"class":"amylin","classLabel":"Amylin analogue","targets":["GLP-1 receptor","Amylin receptors (calcitonin receptor with RAMP proteins)","Calcitonin receptor"],"summarySimple":"Amycretin is an experimental medicine from Novo Nordisk that copies two hormones in a single molecule: GLP-1 and amylin. Both help you feel full and help control blood sugar. It is not approved anywhere yet. Large phase 3 trials for weight loss, type 2 diabetes and heart failure are now running.","summaryExpert":"Amycretin (NNC0487-0111; called zenagamtide in 2026 publications and trial records) is a unimolecular peptide agonist of the GLP-1, amylin and calcitonin receptors, developed by Novo Nordisk. It is a 68-amino-acid peptide of average molecular weight about 7,847 Da: a GLP-1 receptor agonist moiety and an amylin receptor agonist moiety are joined by a linker of four glycine residues and one glutamic acid. It carries a C18 diacid side chain on the GLP-1 lysine at position 37 (GLP-1 7-37 numbering) for reversible albumin binding, a C-terminal amide, and 2-aminoisobutyric acid in the N-terminal GLP-1 region to resist DPP-4 cleavage. Subcutaneous once-weekly and oral once-daily formulations are in clinical development. In humans, the geometric mean terminal half-life after a single subcutaneous dose was 88 hours in adults with normal kidney function, and plasma exposure was dose-proportional in phase 1. Amycretin has no marketing authorisation from any regulator as of 2026-09-29. Key published trials: a first-in-human phase 1 study (NCT05369390); a phase 1b/2a subcutaneous study in overweight or obesity (NCT06064006; body-weight change of -24.3% versus -1.1% with placebo at week 36 at the highest dose tested); and a 36-week phase 2 trial in type 2 diabetes (NCT06542874; HbA1c change from baseline up to -1.7% subcutaneous and -1.4% oral). Phase 3 trials began in 2026: the AMAZE programme (including obesity, obesity with type 2 diabetes, head-to-head trials against semaglutide, obstructive sleep apnoea, knee osteoarthritis and an oral obesity trial) and a separate heart-failure-with-obesity outcomes trial (HF-POLARIS, NCT07567001). No phase 3 efficacy results have been published.","evidence":{"level":"phase2","note":"Human evidence comes from phase 1 and phase 2 trials, all sponsored by Novo Nordisk: a first-in-human phase 1 trial of the oral form (144 adults with overweight or obesity), a phase 1b/2a subcutaneous trial (125 adults, up to 36 weeks), and one 36-week phase 2 trial in type 2 diabetes (NCT06542874) with subcutaneous and oral parts reported in two papers (262 and 186 randomised adults). These are placebo-controlled but small and short, and the phase 1b/2a study had many discontinuations. Phase 3 (AMAZE) trials began in 2026; no phase 3 results are published. Preclinical work in mice and rats is animal-only.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/40550229/","title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1, double-blind, randomised, placebo-controlled trial","publisher":"The Lancet (via PubMed)","date":"2025-06-20","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40550231/","title":"Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study","publisher":"The Lancet (via PubMed)","date":"2025-06-20","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42532080/","title":"Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial","publisher":"The Lancet (via PubMed)","date":"2026-07-30","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42532079/","title":"Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial","publisher":"The Lancet (via PubMed)","date":"2026-07-30","accessed":"2026-09-29"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12309853/","title":"The effect of amycretin, a unimolecular glucagon-like peptide-1 and amylin receptor agonist, on body weight and metabolic dysfunction in mice and rats","publisher":"EBioMedicine (via PubMed Central)","date":"2025-07-23","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT07339423","title":"AMAZE 1: Efficacy and Safety of NNC0487-0111 s.c. Once-weekly in Participants With Obesity (NCT07339423)","publisher":"ClinicalTrials.gov (Novo Nordisk A/S)","date":"2026-01-14","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT07567001","title":"Efficacy and Safety of NNC0487-0111 Compared to Placebo on Morbidity and Mortality in People With Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity (NCT07567001)","publisher":"ClinicalTrials.gov (Novo Nordisk A/S)","date":"2026-05-05","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT07720271","title":"AMAZE 9: Efficacy and Safety of Once-daily Oral Zenagamtide in Participants With Obesity (NCT07720271)","publisher":"ClinicalTrials.gov (Novo Nordisk A/S)","date":"2026-07-22","accessed":"2026-09-29"}],"label":"Phase 2 trials"},"route":"Investigational only. In clinical trials it has been studied as a once-weekly subcutaneous injection (pre-filled pen in the phase 3 trials) and as a once-daily oral tablet. No route is approved for routine use.","halfLife":{"value":"About 88 hours (about 3.7 days): geometric mean terminal half-life after a single subcutaneous dose in adults with normal kidney function (88.1 h); 94 to 113 h across mild to end-stage kidney impairment.","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13538736/","title":"Renal Impairment Does Not Affect Pharmacokinetics, Safety or Tolerability of Zenagamtide","publisher":"Diabetes, Obesity and Metabolism (via PubMed Central)","date":"2026-07-13","accessed":"2026-09-29"}},"structure":{"pubchemCid":null,"pdb":[]},"companies":["novo-nordisk"],"keyFacts":[{"label":"Regulatory status","value":"Investigational: described as still in development for weight management and type 2 diabetes in 2026 peer-reviewed papers; registered trials are investigational and none has reported phase 3 results. No marketing approval from any regulator was found as of 2026-09-29.","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13538736/","title":"Renal Impairment Does Not Affect Pharmacokinetics, Safety or Tolerability of Zenagamtide","publisher":"Diabetes, Obesity and Metabolism (via PubMed Central)","date":"2026-07-13","accessed":"2026-09-29"}},{"label":"Phase 1b/2a weight change (obesity, subcutaneous)","value":"Estimated body-weight change of -24.3% versus -1.1% with placebo at week 36 at the highest dose tested; -22.0% versus +1.9% in another 36-week cohort (125 adults randomised; many discontinuations).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40550231/","title":"Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study","publisher":"The Lancet (via PubMed)","date":"2025-06-20","accessed":"2026-09-29"}},{"label":"Phase 2 HbA1c (type 2 diabetes)","value":"Subcutaneous part (262 adults randomised): HbA1c change from -0.9% to -1.7% by dose at week 36 (mean baseline 7.8%); differences versus placebo of -0.77 to -1.56 percentage points. The oral part of the same trial is reported in a separate paper.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42532080/","title":"Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial","publisher":"The Lancet (via PubMed)","date":"2026-07-30","accessed":"2026-09-29"}},{"label":"Phase 3 programme (AMAZE)","value":"AMAZE 1 (obesity; about 1,150 participants planned; started 2026-02-24; primary outcome body-weight change at week 84) is recruiting. It is one of several registered phase 3 trials that started in 2026.","source":{"url":"https://clinicaltrials.gov/study/NCT07339423","title":"AMAZE 1: Efficacy and Safety of NNC0487-0111 s.c. Once-weekly in Participants With Obesity (NCT07339423)","publisher":"ClinicalTrials.gov (Novo Nordisk A/S)","date":"2026-01-14","accessed":"2026-09-29"}},{"label":"Molecular weight","value":"About 7,847 Da (68 amino acids, average molecular weight).","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12309853/","title":"The effect of amycretin, a unimolecular glucagon-like peptide-1 and amylin receptor agonist, on body weight and metabolic dysfunction in mice and rats","publisher":"EBioMedicine (via PubMed Central)","date":"2025-07-23","accessed":"2026-09-29"}},{"label":"Oral formulation (company-reported)","value":"Phase 1 oral results: mean weight loss of 13.1% versus 1.2% with placebo after 12 weeks at the highest oral dose tested (an exploratory endpoint of the first-in-human trial); the company stated that no weight-loss plateau was seen by the end of treatment.","source":{"url":"https://www.prnewswire.com/news-releases/novo-nordisk-advances-early-stage-obesity-medication-amycretin-to-phase-3-clinical-development-based-on-early-phase-clinical-trial-results-in-people-with-obesity-or-excess-weight-published-in-the-lancet-302487500.html","title":"Novo Nordisk advances early-stage obesity medication, amycretin, to phase 3 clinical development based on early-phase clinical trial results in people with obesity or excess weight, published in The Lancet","publisher":"Novo Nordisk (PR Newswire)","date":"2025-06-20","accessed":"2026-09-29"}}],"safety":[{"text":"First-in-human phase 1 (144 adults): 364 treatment-emergent adverse events in 89 participants (62%); all were mild or moderate and became more frequent with higher doses. Gastrointestinal events were most common (49% of events). No deaths.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40550229/","title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1, double-blind, randomised, placebo-controlled trial","publisher":"The Lancet (via PubMed)","date":"2025-06-20","accessed":"2026-09-29"}},{"text":"Phase 1b/2a (125 adults): the most common adverse events were gastrointestinal, mostly mild to moderate; many participants withdrew, a high proportion for reasons unrelated to adverse events. Rates were described as similar to early-phase studies of GLP-1 and amylin agonists.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40550231/","title":"Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study","publisher":"The Lancet (via PubMed)","date":"2025-06-20","accessed":"2026-09-29"}},{"text":"Phase 2 subcutaneous trial in type 2 diabetes: most adverse events were gastrointestinal and mild to moderate; serious adverse events occurred in 21 of 261 participants (8%), including 3 on placebo. No deaths.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42532080/","title":"Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial","publisher":"The Lancet (via PubMed)","date":"2026-07-30","accessed":"2026-09-29"}},{"text":"Phase 2 oral trial in type 2 diabetes: gastrointestinal adverse events occurred in 26%, 41% and 47% across the three dose groups versus 23% with placebo; serious adverse events in 7 participants on zenagamtide (reported as 4% of the 186 randomised) and none on placebo. No deaths.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42532079/","title":"Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial","publisher":"The Lancet (via PubMed)","date":"2026-07-30","accessed":"2026-09-29"}},{"text":"Single-dose study in kidney impairment (42 adults): 71% had an adverse event, most often decreased appetite, nausea and vomiting; all mild or moderate, none serious. The authors note the small sample and that the single dose used was lower than the doses being tested in development.","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13538736/","title":"Renal Impairment Does Not Affect Pharmacokinetics, Safety or Tolerability of Zenagamtide","publisher":"Diabetes, Obesity and Metabolism (via PubMed Central)","date":"2026-07-13","accessed":"2026-09-29"}}],"related":["cagrilintide","semaglutide","pramlintide","eloralintide"],"lastVerified":"2026-09-29"},{"slug":"aod-9604","name":"AOD-9604","url":"https://glp1base.com/molecules/aod-9604","aliases":["AOD9604","Tyr-hGH(177-191)","Modified C-terminal fragment of human growth hormone (residues 177-191 plus an N-terminal tyrosine)"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["Not established. It does not bind the growth hormone receptor in cell assays; in mice its fat-burning effect depended at least in part on intact beta-3 adrenergic receptor signalling"],"summarySimple":"AOD-9604 is a short piece of human growth hormone that a company tested as a possible weight-loss drug. It helped obese mice and rats. But in the biggest human trial it did not cause enough weight loss, and the company stopped in 2007. It is not an approved medicine, and it is banned in sport.","summaryExpert":"AOD-9604 is a synthetic hexadecapeptide: residues 177-191 of human growth hormone (hGH) with an extra N-terminal tyrosine, and a disulfide bond between the two cysteines (positions 7 and 14 of the 16-residue chain). Molecular formula C78H123N23O23S2, about 1815 Da. It was developed by Metabolic Pharmaceuticals (Australia) as an oral anti-obesity agent, on the idea that the C-terminal lipolytic region of hGH could be separated from hGH's diabetogenic and growth-promoting effects. In cell assays it neither displaces hGH from the growth hormone receptor nor stimulates receptor-driven proliferation; in obese mice and rats it increased fat oxidation and lipolysis without the hyperglycaemia seen with hGH, and mice lacking the beta-3 adrenergic receptor did not respond to chronic treatment. The molecular target has not been identified. No human pharmacokinetic study has been published: in pigs the intravenous half-life was about 3 minutes, and in rat plasma in vitro about 4 minutes, with rapid N-terminal truncation. Company-sponsored human work comprised six randomised, placebo-controlled studies (intravenous and oral, 893 participants in total by the studies' listed sizes); a 12-week phase 2 study reported only a small, non-linear effect on weight (the company later said the best dose fell short of significance on the primary analysis, p=0.1, reaching it only in women), and the 24-week phase 2b OPTIONS study (536 enrolled, 502 randomised) did not reach statistical significance on weight loss at 12 or 24 weeks, so development for obesity was terminated in February 2007. The phase 2b results were announced by the company but do not appear to have been published in a peer-reviewed journal. Later interest in joint cartilage rests on one rabbit study. No regulator among those checked has approved AOD-9604: the US FDA notes it is not a component of any FDA-approved drug; FDA staff recommended against adding it to the 503A bulk drug substances list, its Pharmacy Compounding Advisory Committee voted 12 to 0 against in December 2024, and FDA lists it among bulk substances that may present significant safety risks in compounding. It is prohibited at all times under the WADA 2026 Prohibited List (S2.2.3). Status at EMA, MHRA, PMDA, NMPA, TGA and Health Canada was not verified here.","evidence":{"level":"phase2","note":"The best human evidence is company-sponsored: six randomised, placebo-controlled studies in about 900 people, ending with a 24-week phase 2b obesity trial (OPTIONS, 536 enrolled) that did not show statistically significant weight loss versus placebo at 12 or 24 weeks. The company announced this in 2007 and stopped development for obesity; the phase 2b results do not appear to have been published in a peer-reviewed journal. An earlier 12-week study reported about 2.6 kg loss versus 0.8 kg with placebo in its best dose group, with a non-linear dose response; the company later stated that this difference fell short of statistical significance on the primary analysis (p=0.1) and was significant only in the female subgroup. There are no published human pharmacokinetic studies and no human data for injected (subcutaneous) or skin-applied use. Evidence for effects on fat metabolism, and on cartilage in a rabbit knee model, is animal-only. Use for osteoarthritis, muscle building or other purposes is unapproved and unsupported by human trial data.","sources":[{"url":"https://www.fda.gov/media/183584/download","title":"FDA Briefing Document: Pharmacy Compounding Advisory Committee, evaluation of AOD-9604-related bulk drug substances (AOD-9604 free base and AOD-9604 acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-12","accessed":"2026-09-29"},{"url":"https://www.sec.gov/Archives/edgar/vprr/0702/07021963.pdf","title":"Metabolic Pharmaceuticals Limited: ASX announcement, obesity drug Phase 2B clinical trial results (filed with the SEC as a foreign private issuer submission)","publisher":"Australian Securities Exchange / Metabolic Pharmaceuticals Limited","date":"2007-02-21","accessed":"2026-09-29"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3584306/","title":"Obesity pharmacotherapy: current perspectives and future directions (Misra)","publisher":"Current Cardiology Reviews (via PubMed Central)","date":"2013","accessed":"2026-09-29"},{"url":"https://www.jofem.org/index.php/jofem/article/view/157","title":"Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans (Stier, Vos, Kenley)","publisher":"Journal of Endocrinology and Metabolism","date":"2013-04","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15134286/","title":"AOD-9604 Metabolic (Wilding)","publisher":"Curr Opin Investig Drugs (via PubMed)","date":"2004-04","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11673763/","title":"Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment (Heffernan et al.)","publisher":"Int J Obes Relat Metab Disord (via PubMed)","date":"2001-10","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26275694/","title":"Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model (Kwon and Park)","publisher":"Ann Clin Lab Sci (via PubMed)","date":"2015","accessed":"2026-09-29"}],"label":"Phase 2 trials"},"route":"In the human studies it was given as single intravenous doses, and by mouth either as single doses or once daily for up to 24 weeks. No route is approved. FDA found no human data for subcutaneous injection or skin (transdermal) use.","halfLife":{"value":"Not measured in humans. Animal and laboratory data only: about 3 minutes after an intravenous dose in pigs, and about 4 minutes when added to rat plasma in vitro.","source":{"url":"https://jofem.org/index.php/jofem/article/view/213/278","title":"Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health (More, Kenley)","publisher":"Journal of Endocrinology and Metabolism","date":"2014-06","accessed":"2026-09-29"}},"structure":{"pubchemCid":71300630,"pdb":[]},"companies":[],"keyFacts":[{"label":"Structure","value":"16-amino-acid peptide: hGH residues 177-191 plus an N-terminal tyrosine, with one disulfide ring; formula C78H123N23O23S2, molecular weight about 1815 Da","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/71300630","title":"AOD-9604 (PubChem CID 71300630)","publisher":"National Library of Medicine, PubChem","date":"2026","accessed":"2026-09-29"}},{"label":"Phase 2b obesity trial (OPTIONS)","value":"536 enrolled, 502 randomised, 24 weeks, oral; no statistically significant weight loss versus placebo at 12 or 24 weeks","source":{"url":"https://www.fda.gov/media/183584/download","title":"FDA Briefing Document: Pharmacy Compounding Advisory Committee, evaluation of AOD-9604-related bulk drug substances (AOD-9604 free base and AOD-9604 acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-12","accessed":"2026-09-29"}},{"label":"Development ended","value":"On 21 February 2007 the developer announced the phase 2b results did not support commercial viability and that obesity development was terminated","source":{"url":"https://www.sec.gov/Archives/edgar/vprr/0702/07021963.pdf","title":"Metabolic Pharmaceuticals Limited: ASX announcement, obesity drug Phase 2B clinical trial results (filed with the SEC as a foreign private issuer submission)","publisher":"Australian Securities Exchange / Metabolic Pharmaceuticals Limited","date":"2007-02-21","accessed":"2026-09-29"}},{"label":"FDA advisory committee vote","value":"On 4 December 2024 the FDA Pharmacy Compounding Advisory Committee voted 12 No, 0 Yes on placing AOD-9604 (free base and acetate) on the 503A bulk drug substances list","source":{"url":"https://www.fda.gov/media/185642/download","title":"Summary Minutes: December 4, 2024 Meeting of the Pharmacy Compounding Advisory Committee","publisher":"U.S. Food and Drug Administration","date":"2025-02","accessed":"2026-09-29"}},{"label":"Sport","value":"Named as a prohibited growth hormone fragment (S2.2.3) on the WADA 2026 Prohibited List, banned at all times","source":{"url":"https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf","title":"World Anti-Doping Code International Standard: Prohibited List 2026","publisher":"World Anti-Doping Agency","date":"2025-09","accessed":"2026-09-29"}},{"label":"Human safety dataset","value":"Six sponsor-funded randomised placebo-controlled studies (intravenous and oral); authors reported no significant IGF-1 change and no antibodies in the subsets tested","source":{"url":"https://www.jofem.org/index.php/jofem/article/view/157","title":"Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans (Stier, Vos, Kenley)","publisher":"Journal of Endocrinology and Metabolism","date":"2013-04","accessed":"2026-09-29"}}],"safety":[{"text":"The human safety record comes from six short, company-sponsored studies. FDA reviewers said the published summaries lacked detail on adverse events and lab values, found no human pharmacokinetic data, and concluded there is insufficient information to support long-term safety.","source":{"url":"https://www.fda.gov/media/183584/download","title":"FDA Briefing Document: Pharmacy Compounding Advisory Committee, evaluation of AOD-9604-related bulk drug substances (AOD-9604 free base and AOD-9604 acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-12","accessed":"2026-09-29"}},{"text":"In the oral studies, headache, diarrhoea and flatulence were the most commonly reported adverse events; one case of diarrhoea reported as serious was judged possibly related. In one 7-day study, the highest oral dose group had more headaches, diarrhoea and flatulence.","source":{"url":"https://www.fda.gov/media/183584/download","title":"FDA Briefing Document: Pharmacy Compounding Advisory Committee, evaluation of AOD-9604-related bulk drug substances (AOD-9604 free base and AOD-9604 acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-12","accessed":"2026-09-29"}},{"text":"In intravenous studies, a severe episode of chest tightness in one participant and mild-to-moderate euphoria in five (none on placebo) were judged possibly related to AOD-9604.","source":{"url":"https://www.fda.gov/media/183584/download","title":"FDA Briefing Document: Pharmacy Compounding Advisory Committee, evaluation of AOD-9604-related bulk drug substances (AOD-9604 free base and AOD-9604 acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-12","accessed":"2026-09-29"}},{"text":"In a 12-week oral study of 300 adults, five participants reported serious adverse events that were skin, breast or fatty tumours (basal cell carcinoma, squamous cell carcinoma, lipoma, breast cancer, malignant melanoma), which the investigators judged unrelated to the peptide; FDA said the information was insufficient to rule out a relationship.","source":{"url":"https://www.fda.gov/media/183584/download","title":"FDA Briefing Document: Pharmacy Compounding Advisory Committee, evaluation of AOD-9604-related bulk drug substances (AOD-9604 free base and AOD-9604 acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-12","accessed":"2026-09-29"}},{"text":"FDA lists AOD-9604 among bulk substances that may pose significant safety risks in compounding: possible immunogenicity depending on route, peptide impurities and poor characterisation, and serious adverse events that may be associated with it, though causality is not clear.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}},{"text":"In its 2024 review, FDA judged AOD-9604 not well characterised physically and chemically: the certificates of analysis supplied with the nominations did not report full testing for impurities, aggregates and microbial limits, and some did not control bacterial endotoxin.","source":{"url":"https://www.fda.gov/media/183584/download","title":"FDA Briefing Document: Pharmacy Compounding Advisory Committee, evaluation of AOD-9604-related bulk drug substances (AOD-9604 free base and AOD-9604 acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-12","accessed":"2026-09-29"}},{"text":"Animal-only signals: in the company's published toxicology studies, FDA reviewers flagged dose-related changes in a bone-turnover marker (osteocalcin) in rats, liver-cell vacuolation in monkeys, and equivocal genotoxicity results. The authors judged these of no toxicological relevance, but FDA said that conclusion should be treated with caution because no data tables were published.","source":{"url":"https://www.fda.gov/media/183584/download","title":"FDA Briefing Document: Pharmacy Compounding Advisory Committee, evaluation of AOD-9604-related bulk drug substances (AOD-9604 free base and AOD-9604 acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-12","accessed":"2026-09-29"}},{"text":"There are no human data on subcutaneous or skin-applied AOD-9604, no human pharmacokinetic data, and no long-term human data.","source":{"url":"https://www.fda.gov/media/183584/download","title":"FDA Briefing Document: Pharmacy Compounding Advisory Committee, evaluation of AOD-9604-related bulk drug substances (AOD-9604 free base and AOD-9604 acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-12","accessed":"2026-09-29"}}],"related":["tesamorelin","sermorelin","cjc-1295","ipamorelin"],"lastVerified":"2026-09-29"},{"slug":"bpc-157","name":"BPC-157","url":"https://glp1base.com/molecules/bpc-157","aliases":["Body Protection Compound-157","Body Protective Compound 157","Bepecin","PL 14736","PL-10","PLD-116","pentadecapeptide BPC 157"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["No confirmed molecular target (laboratory studies report effects on VEGFR2 signalling, the nitric oxide pathway and growth-hormone-receptor expression)"],"summarySimple":"BPC-157 is a short chain of 15 building blocks (amino acids) made in a lab. It copies part of a protein first found in stomach juice. In rats and cells it seems to help tissue repair, but it has never been approved as a medicine anywhere, and only a handful of tiny human studies exist.","summaryExpert":"BPC-157 (\"body protection compound 157\", PL 14736, Bepecin) is a synthetic linear pentadecapeptide, GEPPPGKPADDAGLV (C62H98N16O22, 1419.5 g/mol), reported to be a partial sequence of a gastric-juice protein and first synthesised in Croatia in the early 1990s. It is unmodified: no D-amino acids, lipidation or other half-life engineering. The name is a common name, not a USAN (US Adopted Name), and the free base and the acetate salt are distinct bulk substances. Reported preclinical effects (rats, mice and cell models) include protection against drug-induced gastric and liver lesions, faster healing of tendon injuries and colonic fistulas, and pro-angiogenic activity linked in vitro to VEGFR2-Akt-eNOS signalling and nitric oxide modulation; no molecular target has been identified and dose-response relationships have not been established. In rats and beagle dogs the elimination half-life is under 30 minutes (5.3 min in dogs, 15.2 min in rats after IV dosing); intramuscular bioavailability is about 14-19% in rats and 45-51% in dogs, and the peptide is broken down to small fragments and amino acids. Human pharmacokinetics have not been reported. FDA staff found five small human studies (rectal enema studies in healthy volunteers and in ulcerative colitis, the latter a 53-person randomised trial known only from a meeting abstract that showed no clear benefit; intra-articular use for knee pain; intravesical use for interstitial cystitis; and a two-person intravenous pilot) plus a registered phase 1 oral study with no posted results. No approved product contains it in any country. FDA staff recommended against adding it to the 503A bulks list; an advisory committee voted in July 2026 to recommend it anyway, which is advisory only.","evidence":{"level":"animal","note":"Efficacy evidence is almost entirely from rodent and cell studies, largely from a small number of research groups. A 2025 systematic review found 36 studies, 35 preclinical and 1 human (level IV/V evidence, no randomised trials). FDA staff identified five small human studies: an 8-day rectal enema tolerability study in 24 healthy volunteers (meeting abstracts only), a two-week rectal enema study in ulcerative colitis (53 people randomised; results only in a meeting abstract, with a between-group difference of 1.6 points on a disease activity index, 95% CI -4.84 to 1.62), a retrospective chart review of knee injections, some combined with thymosin beta-4 (17 patients, 16 reached by phone; 14 reported relief), a 12-woman bladder pilot without a control group, and a two-person intravenous pilot, plus a registered phase 1 oral-tablet study planned for 42 people (NCT02637284) with no posted results. None of these can show that BPC-157 works or is safe. No phase 2 or phase 3 trial has been published.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/40756949/","title":"Emerging Use of BPC-157 in Orthopaedic Sports Medicine: A Systematic Review","publisher":"HSS Journal (via PubMed)","date":"2025-07-31","accessed":"2026-09-29"},{"url":"https://www.fda.gov/media/193343/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of BPC-157-Related Bulk Drug Substances (BPC-157 free base and BPC-157 acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34324435/","title":"Intra-Articular Injection of BPC 157 for Multiple Types of Knee Pain","publisher":"Alternative Therapies in Health and Medicine (via PubMed)","date":"2021-07","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39325560/","title":"Effect of BPC-157 on Symptoms in Patients with Interstitial Cystitis: A Pilot Study","publisher":"Alternative Therapies in Health and Medicine (via PubMed)","date":"2024-10","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40131143/","title":"Safety of Intravenous Infusion of BPC157 in Humans: A Pilot Study","publisher":"Alternative Therapies in Health and Medicine (via PubMed)","date":"2025-09","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT02637284","title":"PCO-02 - Safety and Pharmacokinetics Trial (Phase I pilot in healthy volunteers; NCT02637284)","publisher":"ClinicalTrials.gov","date":"2015-12","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40789979/","title":"Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing","publisher":"Current Reviews in Musculoskeletal Medicine (via PubMed)","date":"2025-08-12","accessed":"2026-09-29"}],"label":"Animal studies only"},"route":"No approved route. In the few human studies published so far it was given as a rectal enema (ulcerative colitis and healthy volunteers), by injection into a knee joint, by injection into the bladder wall during cystoscopy, and by intravenous infusions on two consecutive days in two people. Animal studies have used injections and oral administration. Oral, subcutaneous, nasal and skin-cream products have not been studied in humans in the literature FDA reviewed. Human bioavailability is unknown.","halfLife":{"value":"Under 30 minutes in rats and beagle dogs (5.3 min in dogs, 15.2 min in rats after an intravenous dose). Not measured in humans.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/36588717/","title":"Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157, a potential drug for treating various wounds, in rats and dogs","publisher":"Frontiers in Pharmacology (via PubMed)","date":"2022-12-14","accessed":"2026-09-29"}},"structure":{"pubchemCid":9941957,"pdb":[]},"companies":[],"keyFacts":[{"label":"Approval status","value":"No approved medicine contains BPC-157 in any country, and it is not in the European, Japanese or International Pharmacopoeias. FDA staff recommended against adding it to the 503A compounding bulks list (FDA staff review, 2026).","source":{"url":"https://www.fda.gov/media/193343/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of BPC-157-Related Bulk Drug Substances (BPC-157 free base and BPC-157 acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"label":"Structure","value":"15 amino acids (GEPPPGKPADDAGLV), C62H98N16O22, 1419.5 g/mol; the name is a common name, not a USAN.","source":{"url":"https://www.fda.gov/media/193343/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of BPC-157-Related Bulk Drug Substances (BPC-157 free base and BPC-157 acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"label":"Half-life (animals)","value":"5.3 minutes in dogs and 15.2 minutes in rats after an intravenous dose; not measured in humans.","source":{"url":"https://www.fda.gov/media/193343/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of BPC-157-Related Bulk Drug Substances (BPC-157 free base and BPC-157 acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"label":"Only randomised human study found by FDA","value":"53 people with ulcerative colitis, 1:1 BPC-157 enema vs placebo for 2 weeks; mean change in disease activity index -3.2 vs -1.6, difference 1.6 points (95% CI -4.84 to 1.62). Available only as a meeting abstract; FDA called it inadequate to support efficacy or safety.","source":{"url":"https://www.fda.gov/media/193343/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of BPC-157-Related Bulk Drug Substances (BPC-157 free base and BPC-157 acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"label":"Published human evidence in orthopaedics","value":"A 2025 systematic review found 36 studies (35 preclinical, 1 clinical) and reported that no clinical safety data were found.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40756949/","title":"Emerging Use of BPC-157 in Orthopaedic Sports Medicine: A Systematic Review","publisher":"HSS Journal (via PubMed)","date":"2025-07-31","accessed":"2026-09-29"}},{"label":"FDA compounding advisory committee, July 2026","value":"At its July 23-24, 2026 meeting the Pharmacy Compounding Advisory Committee voted to recommend adding BPC-157 to the 503A bulks list. The vote is not binding on FDA, and pharmacies may not compound it until final rulemaking is in place.","source":{"url":"https://ncpa.org/newsroom/qam/2026/07/31/fda-advisory-committee-nominates-six-peptides-pharmacies-compound","title":"FDA advisory committee nominates six peptides for pharmacies to compound","publisher":"National Community Pharmacists Association","date":"2026-07-31","accessed":"2026-09-29"}}],"safety":[{"text":"Human safety is not established. FDA staff found five small human studies with no serious adverse events reported, but they were short, tiny, and gave limited safety information; FDA concluded there is insufficient clinical safety information to characterise the safety profile.","source":{"url":"https://www.fda.gov/media/193343/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of BPC-157-Related Bulk Drug Substances (BPC-157 free base and BPC-157 acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"The most common events reported in abstracts from healthy volunteers given a rectal enema were headache and flatulence.","source":{"url":"https://www.fda.gov/media/193343/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of BPC-157-Related Bulk Drug Substances (BPC-157 free base and BPC-157 acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"FDA's adverse-event database contains reports naming BPC-157 (injection site reaction, shortness of breath, diffuse skin hyperpigmentation and gum darkening); FDA could not tell whether the product caused them.","source":{"url":"https://www.fda.gov/media/193343/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of BPC-157-Related Bulk Drug Substances (BPC-157 free base and BPC-157 acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"FDA is concerned about immunogenicity (immune reactions to the peptide) for injected and nasal forms, because peptides can clump together (aggregate) and contain peptide-related impurities. No study has formally tested BPC-157 immunogenicity.","source":{"url":"https://www.fda.gov/media/193343/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of BPC-157-Related Bulk Drug Substances (BPC-157 free base and BPC-157 acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"Animal safety data are limited to 28-day intramuscular studies in rats and dogs, genotoxicity tests (negative) and one rat pregnancy study (no malformations). FDA noted that the 28-day studies appeared to show clinically relevant signals, including changes in a clotting test (aPTT) and liver-related signals (raised ALT, glucose and triglycerides). FDA found no carcinogenicity studies and no toxicity studies by oral, rectal, subcutaneous or nasal routes.","source":{"url":"https://www.fda.gov/media/193343/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of BPC-157-Related Bulk Drug Substances (BPC-157 free base and BPC-157 acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"Adverse effects are possible from unregulated manufacturing, contamination and unknown clinical safety.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40756949/","title":"Emerging Use of BPC-157 in Orthopaedic Sports Medicine: A Systematic Review","publisher":"HSS Journal (via PubMed)","date":"2025-07-31","accessed":"2026-09-29"}},{"text":"FDA's 2026 review notes that BPC-157 is on the World Anti-Doping Agency prohibited list, under non-approved substances (S0).","source":{"url":"https://www.fda.gov/media/193343/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of BPC-157-Related Bulk Drug Substances (BPC-157 free base and BPC-157 acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}}],"related":["tb-500","ghk-cu","kpv","ll-37"],"lastVerified":"2026-09-29"},{"slug":"bremelanotide","name":"Bremelanotide (PT-141)","url":"https://glp1base.com/molecules/bremelanotide","aliases":["PT-141","Bremelanotide acetate","Bremelanotida"],"brands":[{"name":"Vyleesi","company":"palatin-technologies","indication":"Acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women (US). Developed by Palatin; the current US label is held by Cosette Pharmaceuticals."}],"class":"peptide-approved","classLabel":"Approved peptide medicine","targets":["Melanocortin receptors (MC4R and MC1R most relevant at therapeutic exposure; also MC3R, MC5R, MC2R)"],"summarySimple":"Bremelanotide is a small ring-shaped peptide that switches on melanocortin receptors, which are docking points for a natural brain-and-skin hormone. In the US it is a prescription injection for one condition: low sexual desire that causes distress in women before menopause. Doctors do not know exactly how it works.","summaryExpert":"Bremelanotide (formerly PT-141) is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, closed by a lactam bridge between the Asp and Lys side chains (C50H68N14O10, about 1025 Da). It is a non-selective melanocortin receptor agonist with potency order MC1R > MC4R > MC3R > MC5R > MC2R; MC4R and MC1R binding is considered most relevant at therapeutic exposure, and the label states that the mechanism by which it improves HSDD is unknown. After subcutaneous injection absolute bioavailability is about 100%, median Tmax about 1 hour, protein binding 21%, and terminal half-life about 2.7 hours; it is cleared by hydrolysis of amide bonds, with radioactivity recovered mainly in urine (64.8%) and faeces (22.8%). The FDA approved Vyleesi (NDA 210557, sponsor AMAG, later Cosette) on 21 June 2019 for premenopausal women with acquired, generalized HSDD; it is not indicated for postmenopausal women, men or to enhance performance. Approval rested on the two 24-week RECONNECT phase 3 trials (n=1,267 randomised), where the desire-domain gain over placebo was 0.35 points (integrated analysis) and distress fell by 0.33 points; nausea (40% vs 1%), flushing and headache were the main adverse events. It is contraindicated in uncontrolled hypertension or known cardiovascular disease because each use transiently raises blood pressure. A cryo-EM structure of bremelanotide bound to MC4R and Gs is in the PDB (7F55). Approval status at regulators other than the FDA was not verified for this record.","evidence":{"level":"approved","note":"Approved by the US FDA in 2019 on the strength of two identical 24-week randomised, double-blind, placebo-controlled phase 3 trials (RECONNECT, NCT02333071 and NCT02338960; 1,267 women randomised), preceded by a 12-week phase 2 dose-finding trial (NCT01382719). Benefits were modest: the FDA reported that about 25% of treated women had a desire-score increase of 1.2 or more versus about 17% on placebo, and about 35% versus 31% had a distress-score decrease of 1 or more; there was no difference in satisfying sexual events. An intranasal form was studied earlier in healthy men and men with erectile dysfunction; use in men is not approved (the label states it is not indicated in men). The pivotal evidence is in premenopausal women only.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/31599840/","title":"Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials","publisher":"Obstetrics & Gynecology (PubMed)","date":"2019-11","accessed":"2026-09-29"},{"url":"https://www.prnewswire.com/news-releases/fda-approves-new-treatment-for-hypoactive-sexual-desire-disorder-in-premenopausal-women-300872998.html","title":"FDA approves new treatment for hypoactive sexual desire disorder in premenopausal women","publisher":"U.S. Food and Drug Administration (news release distributed via PR Newswire)","date":"2019-06-21","accessed":"2026-09-29"},{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf","title":"VYLEESI (bremelanotide injection) prescribing information, initial approval label (NDA 210557)","publisher":"U.S. Food and Drug Administration (Drugs@FDA)","date":"2019-06","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27181790/","title":"Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial","publisher":"Women's Health (London) (PubMed)","date":"2016-06","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/14963471/","title":"Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141 in healthy males and patients with mild-to-moderate erectile dysfunction","publisher":"International Journal of Impotence Research (PubMed)","date":"2004-02","accessed":"2026-09-29"}],"label":"Approved"},"route":"Subcutaneous injection, self-administered with a single-dose prefilled autoinjector, used as needed ahead of anticipated sexual activity rather than as a daily medicine. It is not taken by mouth. (Earlier clinical studies also tested an intranasal form in men; that form is not approved.)","halfLife":{"value":"About 2.7 hours after a single subcutaneous injection (range 1.9-4.0 hours); median time to peak level about 1 hour","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf","title":"VYLEESI (bremelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Cosette Pharmaceuticals)","date":"2025-11-13","accessed":"2026-09-29"}},"structure":{"pubchemCid":9941379,"pdb":[{"id":"7F55","description":"Cryo-EM structure (3.1 A) of human melanocortin-4 receptor (MC4R) bound to bremelanotide and the Gs G-protein/Nb35 nanobody complex; it shows how the ring-shaped peptide sits in the receptor's binding pocket. Published in Cell Research, 2021."}]},"companies":["palatin-technologies"],"keyFacts":[{"label":"US approval","value":"Approved by the FDA on 21 June 2019 (Vyleesi, NDA 210557) for acquired, generalized HSDD in premenopausal women; not indicated for postmenopausal women, men, or to enhance sexual performance.","source":{"url":"https://www.prnewswire.com/news-releases/fda-approves-new-treatment-for-hypoactive-sexual-desire-disorder-in-premenopausal-women-300872998.html","title":"FDA approves new treatment for hypoactive sexual desire disorder in premenopausal women","publisher":"U.S. Food and Drug Administration (news release distributed via PR Newswire)","date":"2019-06-21","accessed":"2026-09-29"}},{"label":"Developer and licensee","value":"Developed by Palatin Technologies; the NDA was held by AMAG Pharmaceuticals at approval under a North American licence.","source":{"url":"https://palatin.com/press_releases/fda-approves-new-drug-application-for-vyleesi-bremelanotide-injection-2/","title":"FDA Approves New Drug Application for Vyleesi (bremelanotide injection)","publisher":"Palatin Technologies","date":"2019-06-21","accessed":"2026-09-29"}},{"label":"Phase 3 desire result","value":"RECONNECT (n=1,267 randomised): the change in the Female Sexual Function Index desire domain versus placebo was 0.30 (study 301), 0.42 (study 302) and 0.35 (integrated); distress item change versus placebo was -0.37, -0.29 and -0.33.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/31599840/","title":"Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials","publisher":"Obstetrics & Gynecology (PubMed)","date":"2019-11","accessed":"2026-09-29"}},{"label":"Responder rates (FDA)","value":"About 25% of treated women had a desire-score increase of 1.2 or more versus about 17% on placebo; no difference in satisfying sexual events between groups.","source":{"url":"https://www.prnewswire.com/news-releases/fda-approves-new-treatment-for-hypoactive-sexual-desire-disorder-in-premenopausal-women-300872998.html","title":"FDA approves new treatment for hypoactive sexual desire disorder in premenopausal women","publisher":"U.S. Food and Drug Administration (news release distributed via PR Newswire)","date":"2019-06-21","accessed":"2026-09-29"}},{"label":"Half-life","value":"Terminal half-life about 2.7 hours after subcutaneous injection; absolute bioavailability about 100%.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf","title":"VYLEESI (bremelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Cosette Pharmaceuticals)","date":"2025-11-13","accessed":"2026-09-29"}},{"label":"Molecular weight","value":"Molecular formula C50H68N14O10; molecular weight about 1025.2 (free base); cyclic heptapeptide.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf","title":"VYLEESI (bremelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Cosette Pharmaceuticals)","date":"2025-11-13","accessed":"2026-09-29"}}],"safety":[{"text":"Contraindicated in patients with uncontrolled hypertension or known cardiovascular disease, because each use causes a transient rise in blood pressure (up to about 6 mmHg systolic and 3 mmHg diastolic in clinical studies) and a fall in heart rate.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf","title":"VYLEESI (bremelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Cosette Pharmaceuticals)","date":"2025-11-13","accessed":"2026-09-29"}},{"text":"Nausea was reported by 40% of treated women versus about 1% on placebo in the pooled phase 3 trials; 8% stopped because of it and 13% received an anti-emetic. Flushing (20.3%), injection site reactions (13.2%) and headache (11.3%) were also common.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf","title":"VYLEESI (bremelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Cosette Pharmaceuticals)","date":"2025-11-13","accessed":"2026-09-29"}},{"text":"Focal hyperpigmentation (face, gums, breasts) was reported in 1% of women in the phase 3 trials, and in 38% in a separate daily-use study; it was more likely in patients with darker skin and was not confirmed to resolve in all patients after stopping.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf","title":"VYLEESI (bremelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Cosette Pharmaceuticals)","date":"2025-11-13","accessed":"2026-09-29"}},{"text":"Discontinuation because of adverse reactions was 18% with bremelanotide versus 2% with placebo in the phase 3 trials; serious adverse reactions were reported in 1.1% versus 0.5%.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf","title":"VYLEESI (bremelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Cosette Pharmaceuticals)","date":"2025-11-13","accessed":"2026-09-29"}},{"text":"Pregnancy: animal studies (dogs and mice, at exposures well above the human level) showed fetal harm or developmental effects, so the label advises effective contraception and stopping if pregnancy is suspected. It may also reduce absorption of some oral medicines taken at the same time.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf","title":"VYLEESI (bremelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Cosette Pharmaceuticals)","date":"2025-11-13","accessed":"2026-09-29"}},{"text":"The approved use is limited to premenopausal women with acquired, generalized HSDD; the label states it is not indicated in postmenopausal women or men or to enhance sexual performance, and that safety and effectiveness have not been established in children, so use outside that indication is unapproved.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf","title":"VYLEESI (bremelanotide injection) prescribing information, initial approval label (NDA 210557)","publisher":"U.S. Food and Drug Administration (Drugs@FDA)","date":"2019-06","accessed":"2026-09-29"}}],"related":["melanotan-ii","setmelanotide"],"lastVerified":"2026-09-29"},{"slug":"cagrilintide","name":"Cagrilintide (and CagriSema)","url":"https://glp1base.com/molecules/cagrilintide","aliases":["AM833","CagriSema (fixed-dose combination of cagrilintide and semaglutide)","Cagrilintide-semaglutide"],"brands":[],"class":"amylin","classLabel":"Amylin analogue","targets":["Amylin receptors (AMY1R, AMY2R, AMY3R)","Calcitonin receptor"],"summarySimple":"Cagrilintide is an experimental drug that copies amylin, a hormone your pancreas makes to help you feel full. It is built to stay in the body for a long time, so in studies it is given once a week. It is not approved anywhere yet. Its maker has asked the US FDA to approve it combined with semaglutide in one product, called CagriSema.","summaryExpert":"Cagrilintide (AM833) is a 37-residue, C-terminally amidated, long-acting amylin analogue from Novo Nordisk. It keeps the human amylin backbone, including the Cys2-Cys7 disulfide, and differs from mature human amylin at six positions (including prolines at 25, 28 and 29 and a Glu14/Arg17 pair); its developers describe it as a stable analogue, in contrast to native amylin's strong tendency to form amyloid fibrils. In the PubChem structure, a C20 fatty diacid is attached through a gamma-glutamic acid linker to the alpha-amino group of the N-terminal lysine; this lipidation is part of what makes it long acting. It is a non-selective agonist of the calcitonin receptor and the three amylin receptors (calcitonin receptor plus RAMP1, RAMP2 or RAMP3). Elimination half-life is about 159-195 h, which supports once-weekly subcutaneous use. In a 26-week phase 2 trial, weight loss across the cagrilintide groups was 6.0%-10.8% versus 3.0% with placebo (trial product estimand). In the phase 3 REDEFINE 1 trial, cagrilintide alone gave 11.5% weight loss at 68 weeks (treatment-policy estimand) versus 3.0% with placebo, and the fixed-dose combination with semaglutide (CagriSema) gave 20.4%. We found no regulatory approval of cagrilintide, alone or combined, as of the access date. Novo Nordisk filed a US NDA for CagriSema on 2025-12-18 and on 2026-09-21 still described CagriSema as investigational, with an FDA decision expected in Q4 2026; and the cagrilintide-alone RENEW phase 3 programme began in November 2025.","evidence":{"level":"phase3","note":"Human evidence is from randomised phase 1b, phase 2 and phase 3 trials sponsored by Novo Nordisk. Most phase 3 data test the fixed-dose combination with semaglutide (CagriSema). Cagrilintide-alone phase 3 data come from a comparison arm inside REDEFINE 1, and the dedicated RENEW 1 and RENEW 2 phase 3 trials had not reported at the access date. Cagrilintide is not approved by any regulator. On 2026-09-21 Novo Nordisk still described CagriSema as an investigational product and said an FDA decision on its December 2025 application is expected in Q4 2026.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/34798060/","title":"Once-weekly cagrilintide for weight management in people with overweight and obesity: a dose-finding phase 2 trial","publisher":"The Lancet (via PubMed)","date":"2021-11-16","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40544433/","title":"Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)","publisher":"New England Journal of Medicine (via PubMed)","date":"2025-06-22","accessed":"2026-09-29"},{"url":"https://www.biospace.com/press-releases/novo-nordisk-presents-phase-3-data-for-next-generation-amylin-cagrilintide-leading-to-advancement-into-dedicated-clinical-programme","title":"Novo Nordisk presents phase 3 data for next-generation amylin cagrilintide, leading to advancement into dedicated clinical programme","publisher":"Novo Nordisk press release (reprinted by BioSpace)","date":"2025-09-16","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT07220642","title":"RENEW 1: Efficacy and Safety of Cagrilintide for Weight Management in Participants With Overweight or Obesity (NCT07220642)","publisher":"ClinicalTrials.gov","date":"2025-10-24","accessed":"2026-09-29"},{"url":"https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916774","title":"Novo's CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial","publisher":"Novo Nordisk (company announcement)","date":"2026-09-21","accessed":"2026-09-29"}],"label":"Phase 3 trials"},"route":"Investigational once-weekly subcutaneous injection in clinical trials, alone or as a fixed-dose combination with semaglutide (CagriSema). There is no approved route because there is no approved product.","halfLife":{"value":"About 159-195 hours (roughly 6.5-8 days) in a phase 1b trial where cagrilintide was given together with semaglutide","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/33894838/","title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide for weight management: a randomised, controlled, phase 1b trial","publisher":"The Lancet (via PubMed)","date":"2021-04-22","accessed":"2026-09-29"}},"structure":{"pubchemCid":171397054,"pdb":[{"id":"7BG0","description":"X-ray crystal structure (2.89 A) of a fusion of maltose-binding protein with the backbone of cagrilintide (AM833), deposited with the J Med Chem paper describing its design. It shows the peptide backbone, not the fatty-acid side chain."},{"id":"9BQ3","description":"Cryo-EM structure (2.8 A) of cagrilintide bound to the human amylin 2 receptor (AMY2R) with Gs protein."},{"id":"9BUB","description":"Cryo-EM structure (2.3 A) of cagrilintide bound to the human calcitonin receptor with Gs protein, in the 'bypass' binding conformation."},{"id":"9BUD","description":"Cryo-EM structure (2.5 A) of cagrilintide bound to the human calcitonin receptor with Gs protein, in a calcitonin-like conformation."},{"id":"9UWQ","description":"Cryo-EM structure (3.1 A) of cagrilintide bound to the human amylin 1 receptor (AMY1R) with Gs protein."},{"id":"9BP3","description":"Human Amylin1 Receptor in complex with Gs and cagrilintide"}]},"companies":["novo-nordisk"],"keyFacts":[{"label":"Regulatory status","value":"No approval by any regulator found as of 2026-09-29. FDA states that cagrilintide is not a component of FDA-approved drugs and has not been found safe and effective for any condition.","source":{"url":"https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss","title":"FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss","publisher":"U.S. Food and Drug Administration","date":"2026-09-01","accessed":"2026-09-29"}},{"label":"CagriSema filing","value":"Novo Nordisk announced on 2025-12-18 that it had filed a US New Drug Application for the once-weekly cagrilintide-semaglutide combination for adult weight management, with FDA review expected in 2026.","source":{"url":"https://www.prnewswire.com/news-releases/novo-nordisk-files-for-fda-approval-of-cagrisema-the-first-once-weekly-combination-of-glp1-and-amylin-analogues-for-weight-management-302645862.html","title":"Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management","publisher":"Novo Nordisk (press release)","date":"2025-12-18","accessed":"2026-09-29"}},{"label":"REDEFINE 1 (68 weeks, adults without diabetes)","value":"Cagrilintide-semaglutide: -20.4% body weight versus -3.0% with placebo (estimated difference -17.3 percentage points; treatment-policy estimand; 3,417 participants).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40544433/","title":"Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)","publisher":"New England Journal of Medicine (via PubMed)","date":"2025-06-22","accessed":"2026-09-29"}},{"label":"Cagrilintide alone, REDEFINE 1","value":"-11.5% versus -3.0% with placebo (treatment-policy estimand); -11.8% versus -2.3% if all participants stayed on treatment.","source":{"url":"https://www.biospace.com/press-releases/novo-nordisk-presents-phase-3-data-for-next-generation-amylin-cagrilintide-leading-to-advancement-into-dedicated-clinical-programme","title":"Novo Nordisk presents phase 3 data for next-generation amylin cagrilintide, leading to advancement into dedicated clinical programme","publisher":"Novo Nordisk press release (reprinted by BioSpace)","date":"2025-09-16","accessed":"2026-09-29"}},{"label":"Phase 2, 26 weeks","value":"Weight reductions of 6.0%-10.8% across cagrilintide groups versus 3.0% with placebo; the highest-dose group also beat daily liraglutide (10.8% versus 9.0%, p=0.03).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/34798060/","title":"Once-weekly cagrilintide for weight management in people with overweight and obesity: a dose-finding phase 2 trial","publisher":"The Lancet (via PubMed)","date":"2021-11-16","accessed":"2026-09-29"}},{"label":"Half-life","value":"159-195 h for cagrilintide given with semaglutide in a phase 1b trial (median time to peak concentration 24-72 h).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/33894838/","title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide for weight management: a randomised, controlled, phase 1b trial","publisher":"The Lancet (via PubMed)","date":"2021-04-22","accessed":"2026-09-29"}},{"label":"Molecular size","value":"Computed molecular weight about 4409 Da (C194H312N54O59S2), a 37-amino-acid lipidated peptide.","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/171397054","title":"Cagrilintide (PubChem CID 171397054)","publisher":"PubChem, National Library of Medicine","date":"2024-06-20","accessed":"2026-09-29"}}],"safety":[{"text":"Phase 2 trial: gastrointestinal adverse events (mainly nausea, constipation, diarrhoea) occurred in 41%-63% of participants on cagrilintide versus 32% on placebo, and administration-site reactions were also frequent.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/34798060/","title":"Once-weekly cagrilintide for weight management in people with overweight and obesity: a dose-finding phase 2 trial","publisher":"The Lancet (via PubMed)","date":"2021-11-16","accessed":"2026-09-29"}},{"text":"REDEFINE 1: gastrointestinal adverse events affected 79.6% of people on cagrilintide-semaglutide versus 39.9% on placebo, mainly transient and mild to moderate.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40544433/","title":"Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)","publisher":"New England Journal of Medicine (via PubMed)","date":"2025-06-22","accessed":"2026-09-29"}},{"text":"Company-reported REDEFINE 1 data: nausea led to permanent discontinuation in 1.0% of people on cagrilintide alone versus 0.1% on placebo.","source":{"url":"https://www.biospace.com/press-releases/novo-nordisk-presents-phase-3-data-for-next-generation-amylin-cagrilintide-leading-to-advancement-into-dedicated-clinical-programme","title":"Novo Nordisk presents phase 3 data for next-generation amylin cagrilintide, leading to advancement into dedicated clinical programme","publisher":"Novo Nordisk press release (reprinted by BioSpace)","date":"2025-09-16","accessed":"2026-09-29"}},{"text":"A thorough QT study in 105 healthy adults found no clinically relevant prolongation of the QTcF interval with cagrilintide compared with placebo.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/39279639/","title":"Cagrilintide is not associated with clinically relevant QTc prolongation: a thorough QT study in healthy participants","publisher":"Diabetes, Obesity and Metabolism (via PubMed)","date":"2024-09-16","accessed":"2026-09-29"}},{"text":"Cagrilintide is not approved by FDA and, per FDA, cannot be used in compounding under federal law; it has not been found safe and effective for any condition.","source":{"url":"https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss","title":"FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss","publisher":"U.S. Food and Drug Administration","date":"2026-09-01","accessed":"2026-09-29"}},{"text":"Unregulated products: US Customs stated that overseas-made unapproved peptides, with cagrilintide listed among those seized in one 2026 case, could be contaminated with other substances or impurities, and that their authenticity and safety cannot be determined.","source":{"url":"https://www.cbp.gov/newsroom/local-media-release/cincinnati-cbp-foils-scheme-smuggle-over-5000-unapproved-peptides-us","title":"Cincinnati CBP foils scheme to smuggle over 5,000 unapproved peptides into the U.S.","publisher":"U.S. Customs and Border Protection","date":"2026-03-31","accessed":"2026-09-29"}}],"related":["semaglutide","pramlintide","amycretin","eloralintide","tirzepatide"],"lastVerified":"2026-09-29"},{"slug":"cjc-1295","name":"CJC-1295","url":"https://glp1base.com/molecules/cjc-1295","aliases":["CJC-1295 DAC","CJC1295","DAC:GRF","Tetrasubstituted GRF(1-29)","Modified GRF(1-29)","Drug Affinity Complex GHRH analogue"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["Growth hormone-releasing hormone receptor (GHRHR) on pituitary somatotroph cells: the receptor the parent hormone GHRH acts on","Serum albumin (Cys34): covalent attachment site for the DAC form, shown in rats and in laboratory conjugation studies","Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) axis: downstream effect measured in healthy adults"],"summarySimple":"CJC-1295 is a lab-made copy of GHRH, a brain hormone that tells the pituitary gland to release growth hormone. One version is built to stick to a blood protein so it lasts about a week. The only published human studies are small, short trials in healthy adults. No regulator has approved it as a medicine.","summaryExpert":"CJC-1295 is a synthetic analogue of human GHRH(1-29), the shortest fully active fragment of growth hormone-releasing hormone. It carries substitutions at positions 2 (D-Ala, which FDA notes may make the peptide resistant to dipeptidyl peptidase-IV), 8 (Gln), 15 (Ala) and 27 (Leu) and a C-terminal amide (Jette 2005; FDA 2024). FDA distinguishes two active moieties that the literature and sellers often conflate: CJC-1295 without DAC (29 residues, C152H252N44O42, about 3368 g/mol) and CJC-1295 with the Drug Affinity Complex (DAC), which adds a C-terminal Lys carrying a 3-maleimidopropionamide group (C165H269N47O46, about 3647 g/mol). The maleimide reacts with the free thiol of Cys34 on serum albumin after injection, giving a long-lived albumin conjugate (shown in rats by Western blot). The DAC form is the one studied in humans. In two randomised, placebo-controlled, double-blind ascending-dose trials in healthy adults aged 21-61 years (Teichman 2006), single subcutaneous injections raised mean plasma GH 2- to 10-fold for 6 days or more and IGF-I 1.5- to 3-fold for 9-11 days; estimated half-life was 5.8-8.1 days and no serious adverse reactions were reported. In a follow-up study in young men (Ionescu and Frohman 2006), pulsatile GH secretion was preserved (pulse frequency and size unchanged) while trough GH rose 7.5-fold, mean GH 46% and IGF-I 45%. Animal data include normalised growth in GHRH-knockout mice with somatotroph proliferation (Alba 2006). A phase 2 trial in HIV-associated visceral obesity (NCT00267527) was terminated in 2006 and its data were never published; FDA describes anecdotal reports that a participant died of a myocardial infarction, which the attending physician attributed to underlying coronary disease. No efficacy trial in growth hormone deficiency or any other disease has been published. CJC-1295 is not a component of any FDA-approved drug and has no USP monograph. In December 2024 FDA's Pharmacy Compounding Advisory Committee voted against placing any CJC-1295 form on the 503A bulks list.","evidence":{"level":"human-small","note":"Human evidence is limited to short studies in healthy adult volunteers. FDA counted 63 healthy adults across three published studies, mostly men, and most received only one injection. These studies measured hormone levels (GH and IGF-I), pharmacokinetics and short-term tolerability, not whether the peptide treats any condition. A phase 2 trial in HIV-associated visceral obesity was registered in 2005 and terminated in 2006 and has no published results. There is no published trial in people with growth hormone deficiency. Growth results come from animals only (rats and GHRH-knockout mice). Long-term safety in humans is unknown.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/16352683/","title":"Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults","publisher":"Journal of Clinical Endocrinology & Metabolism (Teichman SL et al.)","date":"2006-03","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17018654/","title":"Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog","publisher":"Journal of Clinical Endocrinology & Metabolism (Ionescu M, Frohman LA)","date":"2006-12","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT00267527","title":"A Study to Evaluate CJC 1295 in HIV Patients With Visceral Obesity (NCT00267527)","publisher":"ClinicalTrials.gov (ConjuChem)","date":"2005-12","accessed":"2026-09-29"},{"url":"https://www.fda.gov/media/183819/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, December 4, 2024: CJC-1295-Related Bulk Drug Substances","publisher":"U.S. Food and Drug Administration","date":"2024-12-04","accessed":"2026-09-29"}],"label":"Small human studies"},"route":"Not given by any approved route, because it is not approved anywhere. In the published human studies it was given as a subcutaneous (under-the-skin) injection to healthy adult volunteers in supervised trial settings. In animal studies it was given by subcutaneous injection to rats and mice. No trial has established a route or schedule for treating any condition.","halfLife":{"value":"About 5.8 to 8.1 days (estimated after single injections of the DAC form in healthy adults)","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/16352683/","title":"Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults","publisher":"Journal of Clinical Endocrinology & Metabolism (Teichman SL et al.)","date":"2006-03","accessed":"2026-09-29"}},"structure":{"pubchemCid":91971820,"pdb":[{"id":"7CZ5","description":"Cryo-EM structure (2.6 A) of the human GHRH receptor bound to native GHRH (somatoliberin) and the Gs protein. It shows the receptor that CJC-1295 is designed to act on, with the natural hormone bound. It does not contain CJC-1295 itself."}]},"companies":[],"keyFacts":[{"label":"Regulatory status","value":"Not approved as a medicine. FDA states that none of the CJC-1295-related substances is a component of an FDA-approved drug and that there is no USP monograph. FDA found no published study of any CJC-1295 form in people with growth hormone deficiency.","source":{"url":"https://www.fda.gov/media/183819/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, December 4, 2024: CJC-1295-Related Bulk Drug Substances","publisher":"U.S. Food and Drug Administration","date":"2024-12-04","accessed":"2026-09-29"}},{"label":"FDA compounding-safety page (updated 22 Apr 2026)","value":"CJC-1295 appears in the table of bulk drug substances nominated but withdrawn (previously in Category 2), not among active Category 2 entries. FDA repeats its warning of immunogenicity risk and serious adverse events including increased heart rate and systemic vasodilatory reaction.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}},{"label":"Advisory committee vote (4 Dec 2024)","value":"FDA's Pharmacy Compounding Advisory Committee voted 0 yes to 13 no on placing CJC-1295 (free base), CJC-1295 DAC (free base), CJC-1295 DAC acetate and CJC-1295 DAC trifluoroacetate on the 503A bulks list, and 1 yes to 12 no for CJC-1295 acetate. The vote is advisory.","source":{"url":"https://www.fda.gov/media/185641/download","title":"December 4, 2024 Pharmacy Compounding Advisory Committee Meeting Transcript (CJC-1295-related bulk drug substances)","publisher":"U.S. Food and Drug Administration","date":"2024-12-04","accessed":"2026-09-29"}},{"label":"Half-life (DAC form, healthy adults)","value":"Estimated 5.8 to 8.1 days after single subcutaneous injections","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/16352683/","title":"Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults","publisher":"Journal of Clinical Endocrinology & Metabolism (Teichman SL et al.)","date":"2006-03","accessed":"2026-09-29"}},{"label":"Hormone response after a single injection (healthy adults)","value":"Mean plasma GH rose 2- to 10-fold for 6 days or more; mean plasma IGF-I rose 1.5- to 3-fold for 9-11 days","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/16352683/","title":"Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults","publisher":"Journal of Clinical Endocrinology & Metabolism (Teichman SL et al.)","date":"2006-03","accessed":"2026-09-29"}},{"label":"GH pulsatility","value":"Pulse frequency and size unchanged; trough GH up 7.5-fold, mean GH up 46%, IGF-I up 45% one week after injection in healthy men","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/17018654/","title":"Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog","publisher":"Journal of Clinical Endocrinology & Metabolism (Ionescu M, Frohman LA)","date":"2006-12","accessed":"2026-09-29"}}],"safety":[{"text":"FDA states that compounded drugs containing CJC-1295 may pose a risk of immunogenicity for certain routes of administration and may have complexities with peptide-related impurities and API characterization. It says it has identified serious adverse events associated with CJC-1295, including increased heart rate and systemic vasodilatory reaction, and that available clinical data are limited.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}},{"text":"In the published healthy-volunteer studies (63 adults, mostly men, most receiving one injection), injection-site reactions were the most common adverse event. Others included systemic vasodilatory reactions, headache, nausea, abdominal pain, diarrhoea, transient involuntary leg muscle contractions with some loss of coordination, dizziness, low blood pressure and increased heart rate.","source":{"url":"https://www.fda.gov/media/183819/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, December 4, 2024: CJC-1295-Related Bulk Drug Substances","publisher":"U.S. Food and Drug Administration","date":"2024-12-04","accessed":"2026-09-29"}},{"text":"A phase 2 trial in HIV-associated visceral obesity (NCT00267527) was terminated in 2006. FDA cites anecdotal reports that one participant died of a myocardial infarction after a weekly injection; the attending physician attributed it to asymptomatic coronary artery disease with plaque rupture. The data were not published, so the role of the drug is unknown.","source":{"url":"https://www.fda.gov/media/183819/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, December 4, 2024: CJC-1295-Related Bulk Drug Substances","publisher":"U.S. Food and Drug Administration","date":"2024-12-04","accessed":"2026-09-29"}},{"text":"Animal and laboratory toxicity signals reviewed by FDA: in repeat-dose studies of up to 14 days in rats and dogs (published only as abstracts), CJC-1295 DAC caused injection-site haemorrhage, inflammation and necrosis, and DNA-damage (genotoxic) signals were seen in mouse pituitary cell cultures and in the pituitaries of treated mice. No carcinogenicity studies were found, so pituitary overgrowth or tumours with long-term use cannot be ruled out.","source":{"url":"https://www.fda.gov/media/183819/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, December 4, 2024: CJC-1295-Related Bulk Drug Substances","publisher":"U.S. Food and Drug Administration","date":"2024-12-04","accessed":"2026-09-29"}},{"text":"Products sold under the name CJC-1295 can be different substances. FDA identified at least five distinct bulk substances and nine names in use, two of them different active moieties (with and without DAC), and said the inconsistent naming is itself a safety risk. It also found the substances not well characterised, and no safety data in children or on long-term use.","source":{"url":"https://www.fda.gov/media/183819/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, December 4, 2024: CJC-1295-Related Bulk Drug Substances","publisher":"U.S. Food and Drug Administration","date":"2024-12-04","accessed":"2026-09-29"}}],"related":["sermorelin","tesamorelin","ipamorelin"],"lastVerified":"2026-09-29"},{"slug":"dsip","name":"DSIP (delta sleep-inducing peptide)","url":"https://glp1base.com/molecules/dsip","aliases":["Emideltide","Delta sleep-inducing peptide","Delta sleeping inducing peptide","DSIP nonapeptide","Delta sleep peptide"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["No confirmed receptor or molecular target. Animal and cell studies point to an indirect link with the opioid system (naloxone blocks some effects, but DSIP did not displace an opioid ligand from rat brain or human placental membranes in vitro) and to reported release of enkephalins in brain tissue."],"summarySimple":"DSIP is a tiny chain of nine amino acids (the building blocks of proteins). Scientists first found it in rabbit blood in the 1970s during sleep experiments. It is not an approved medicine anywhere we could verify. Human studies were small and old, and results were mixed. Nobody has found its gene or receptor, so how it might work is still unclear.","summaryExpert":"DSIP (delta sleep-inducing peptide; INN emideltide) is a linear nonapeptide, H-Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu-OH (C35H48N10O15, 848.8 g/mol; PubChem CID 68816, CAS 62568-57-4). It was isolated in 1977 by the Schoenenberger-Monnier group in Basel from cerebral venous blood dialysate of rabbits given hypnogenic thalamic stimulation; the synthetic peptide raised EEG delta and spindle activity after intraventricular infusion in rabbits, and only the alpha-aspartyl form (not the beta-Asp isomer) was active. It is unmodified: no D-amino acids, lipidation or other half-life engineering. No gene, precursor protein or receptor has been identified, and a 2006 review called the link between DSIP and sleep weakly documented. In animals the peptide crosses the blood-brain barrier and its sleep effects are inconsistent between studies; naloxone blocks some effects, but DSIP does not displace opioid ligands from receptor membranes in vitro, and enkephalin release has been reported in brain tissue. Pharmacokinetics: plasma half-life after intravenous injection is about 2 to 4 minutes in dogs, a monkey and rats (Kato 1984) and about 5 to 10 minutes in human serum in vitro (as cited by FDA), which FDA attributes mainly to rapid breakdown by peptidases starting at the N-terminal end; FDA identified no pharmacokinetic study for subcutaneous use. Human evidence is limited to 1980s to 1990s intravenous studies: small crossover and parallel-group studies in chronic insomnia with inconsistent results (the 16-patient double-blind study of Bes 1992 concluded any benefit was weak), an uncontrolled open-label report in 107 inpatients with alcohol or opiate withdrawal (Dick 1984), a 7-patient open-label opioid detoxification study (Backmund 1998, as summarised by FDA), and a single-patient narcolepsy report. No phase 2 or 3 programme was identified. No regulator among FDA, EMA, MHRA, PMDA, NMPA, TGA or Health Canada has approved a DSIP product that we could verify; there is no USP or NF monograph. FDA evaluated emideltide-related bulk substances at its own initiative for the 503A bulks list after two nominations were withdrawn, proposed not adding them (poor characterisation, insufficient evidence of effectiveness, no subcutaneous-route effectiveness or safety data, immunogenicity and impurity concerns), and the Pharmacy Compounding Advisory Committee narrowly voted against listing (6 to 7, with 1 abstention) on 24 July 2026.","evidence":{"level":"human-small","note":"Human evidence is small, old and mixed, and all of it used intravenous injection. Chronic insomnia: FDA's 2026 review focused on three studies and also described several other small reports. A 6-person crossover study reported only tendencies toward fewer awakenings and higher sleep efficiency; a 14-person study without a placebo arm (compared with an external matched group) reported shorter time to fall asleep (58.4 to 27.6 minutes) and more total sleep time, but FDA judged its methods poor; and the 16-patient double-blind parallel-group study of Bes 1992 concluded that the statistically significant effects were weak and that short-term treatment is not likely to be of major therapeutic benefit. FDA also noted that a second double-blind, placebo-controlled crossover study in 6 patients (Monti 1987) found no significant differences from placebo. Withdrawal: an uncontrolled open-label report in 107 inpatients with alcohol or opiate withdrawal described improved signs and symptoms, but had no comparison group or blinding; FDA also described a 7-patient open-label opioid detoxification study (Backmund 1998) with no comparison group. Narcolepsy: a single-patient case report. FDA concluded there was insufficient evidence of effectiveness for chronic insomnia, narcolepsy or opioid withdrawal, and none for the subcutaneous route. Animal: rabbit, rat and cat EEG studies report more delta-wave activity, but findings differ between laboratories and some studies found no effect. No phase 2 or phase 3 trial was identified.","sources":[{"url":"https://www.fda.gov/media/193344/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Emideltide-related bulk drug substances (Emideltide (free base) and Emideltide acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/1299794/","title":"Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study","publisher":"Neuropsychobiology (via PubMed)","date":"1992","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/6548969/","title":"DSIP in the treatment of withdrawal syndromes from alcohol and opiates","publisher":"European Neurology (via PubMed)","date":"1984","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/265572/","title":"Characterization of a delta-electroencephalogram (-sleep)-inducing peptide","publisher":"Proceedings of the National Academy of Sciences of the USA (via PubMed)","date":"1977-03","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16539679/","title":"Delta sleep-inducing peptide (DSIP): a still unresolved riddle","publisher":"Journal of Neurochemistry (via PubMed)","date":"2006-04","accessed":"2026-09-29"}],"label":"Small human studies"},"route":"In every human study FDA identified, DSIP was given by intravenous injection in a clinical or laboratory setting. Animal studies also used direct infusion into the brain ventricles, and intraperitoneal or subcutaneous injection. No study of subcutaneous or nasal use in people was identified by FDA. No approved product exists and there is no approved route.","halfLife":{"value":"Very short. In animals, about 2 to 6 minutes after intravenous injection (dogs 3 to 6 minutes; rats and a monkey about 2 to 3 minutes). FDA's 2026 review also states a plasma half-life of about 8 minutes without naming the species or study, and a half-life of about 5 to 10 minutes when the peptide was kept in human serum in a test tube. No human pharmacokinetic data exist for injection under the skin.","source":{"url":"https://www.fda.gov/media/193344/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Emideltide-related bulk drug substances (Emideltide (free base) and Emideltide acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},"structure":{"pubchemCid":68816,"pdb":[]},"companies":[],"keyFacts":[{"label":"Structure","value":"Linear nonapeptide Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, formula C35H48N10O15, molecular weight 848.8 g/mol (PubChem CID 68816; INN emideltide).","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/68816","title":"Delta Sleep-Inducing Peptide (PubChem CID 68816)","publisher":"National Center for Biotechnology Information, PubChem","date":"2026","accessed":"2026-09-29"}},{"label":"Discovery","value":"Isolated in 1977 from rabbit cerebral venous blood after thalamic stimulation; the synthetic peptide enhanced EEG delta and spindle activity when infused into rabbit brains.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/265572/","title":"Characterization of a delta-electroencephalogram (-sleep)-inducing peptide","publisher":"Proceedings of the National Academy of Sciences of the USA (via PubMed)","date":"1977-03","accessed":"2026-09-29"}},{"label":"Half-life in animals","value":"About 4.0 minutes in dogs, 2.9 minutes in a monkey and 2.0 minutes in rats after intravenous injection.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/6379493/","title":"Development of an enzyme immunoassay for delta sleep-inducing peptide (DSIP) and its use in the determination of the metabolic clearance rate of DSIP administered to dogs","publisher":"Neuroendocrinology (via PubMed)","date":"1984-07","accessed":"2026-09-29"}},{"label":"Best controlled human insomnia study","value":"Bes 1992: 16 chronic insomnia patients, double-blind, intravenous DSIP versus glucose placebo; the authors concluded that short-term treatment is not likely to be of major therapeutic benefit.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/1299794/","title":"Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study","publisher":"Neuropsychobiology (via PubMed)","date":"1992","accessed":"2026-09-29"}},{"label":"FDA compounding review","value":"FDA's staff proposed not adding emideltide (free base or acetate) to the 503A bulks list, citing poor characterisation, insufficient evidence of effectiveness for chronic insomnia, narcolepsy or opioid withdrawal, and no effectiveness or safety data for the subcutaneous route. It has no USP monograph and is not in any FDA-approved drug.","source":{"url":"https://www.fda.gov/media/193344/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Emideltide-related bulk drug substances (Emideltide (free base) and Emideltide acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"label":"Advisory committee vote","value":"The Pharmacy Compounding Advisory Committee narrowly voted against recommending emideltide for the list (6 to 7, with 1 abstention) on 24 July 2026. The vote is advice to FDA, not a final decision.","source":{"url":"https://www.raps.org/resource/fda-advisory-committee-backs-two-more-peptides-rejects-one-for-compounding-list.html","title":"FDA advisory committee backs two more peptides, rejects one for compounding list","publisher":"Regulatory Affairs Professionals Society (RAPS)","date":"2026-07-24","accessed":"2026-09-29"}}],"safety":[{"text":"Human safety data are limited to small intravenous studies. FDA counted 209 people given intravenous DSIP for 1 to 15 days across the studies it found, with no significant adverse events reported in chronic insomnia studies. It found no safety data for the subcutaneous route and no reports in its adverse event reporting system through 3 March 2024.","source":{"url":"https://www.fda.gov/media/193344/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Emideltide-related bulk drug substances (Emideltide (free base) and Emideltide acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"In the 107-patient withdrawal report, headache, sweating, nausea and vertigo were noted in some patients, and three had serious effects: two had low blood pressure at the first injection and one had repeated episodes of discomfort with sweating and nausea. FDA said these effects were hard to interpret because withdrawal itself causes similar symptoms.","source":{"url":"https://www.fda.gov/media/193344/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Emideltide-related bulk drug substances (Emideltide (free base) and Emideltide acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"FDA raised concerns that a nine-amino-acid peptide given by injection may cause immune responses, made more likely by aggregation and by peptide-related impurities. It also noted that the free-base form has limited water solubility, which makes formulation unclear. Specific tests for impurities, aggregates and endotoxins were not found in the public literature.","source":{"url":"https://www.fda.gov/media/193344/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Emideltide-related bulk drug substances (Emideltide (free base) and Emideltide acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"Because DSIP may stimulate release of the body's own opioid-like peptides, FDA noted a theoretical risk of reinforcing effects; no studies of abuse potential were found. Drugs that block the enzyme peptidyl dipeptidase A could in principle slow DSIP breakdown (nonclinical data only).","source":{"url":"https://www.fda.gov/media/193344/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Emideltide-related bulk drug substances (Emideltide (free base) and Emideltide acetate) for inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"Health Canada lists DSIP among unauthorized injectable peptide drugs it has seized. It states that such products are illegal, have not been assessed for safety, efficacy and quality, and may contain too much, too little or none of the active ingredient, unlisted ingredients or contaminants.","source":{"url":"https://recalls-rappels.canada.ca/en/alert-recall/think-twice-injecting-peptides-bought-online-unauthorized-products-can-seriously-harm","title":"Think twice before injecting peptides bought online: unauthorized products can seriously harm you","publisher":"Health Canada","date":"2026-04-09","accessed":"2026-09-29"}}],"related":["epitalon","selank","semax"],"lastVerified":"2026-09-29"},{"slug":"dulaglutide","name":"Dulaglutide","url":"https://glp1base.com/molecules/dulaglutide","aliases":["LY2189265","Dulaglutida"],"brands":[{"name":"Trulicity","company":"eli-lilly","indication":"Type 2 diabetes (adults and children aged 10 and older); reducing major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease or multiple risk factors"}],"class":"glp1-approved","classLabel":"Approved GLP-1 medicine","targets":["GLP-1 receptor"],"summarySimple":"Dulaglutide copies a gut hormone called GLP-1. It helps the pancreas release insulin when blood sugar is high and slows how fast the stomach empties. It is joined to part of an antibody, which keeps it in the body for days, so it is given once a week. It is approved for type 2 diabetes.","summaryExpert":"Dulaglutide is a GLP-1 receptor agonist fusion protein: two disulfide-linked chains, each carrying a GLP-1(7-37) analogue (90% homologous to native GLP-1, with changes that resist DPP-4 cleavage) joined by a short peptide linker to a modified human IgG4 Fc fragment engineered to reduce Fc-receptor binding and half-antibody formation. It is produced in Chinese hamster ovary cells and has a molecular weight of about 63 kDa. The Fc fusion gives a much longer half-life than native GLP-1: elimination half-life is about 5 days, time to peak concentration of 24 to 72 hours and steady state after 2 to 4 weeks. It activates the GLP-1 receptor on pancreatic beta cells (cAMP-dependent, glucose-dependent insulin release), lowers glucagon and delays gastric emptying. FDA approved it on 2014-09-18 and the EU authorised it on 2014-11-21, for type 2 diabetes; the label also includes reducing major adverse cardiovascular events, based on REWIND (HR 0.88). It carries a boxed warning for thyroid C-cell tumours seen in rats. Unlike semaglutide and tirzepatide, it is not approved for chronic weight management.","evidence":{"level":"approved","note":"Approved on the AWARD phase 3 programme in type 2 diabetes (for example AWARD-2 versus insulin glargine), then the REWIND cardiovascular outcomes trial (9,901 participants, median follow-up 5.4 years) and the AWARD-PEDS trial in youths aged 10 to under 18. Preclinical engineering and animal studies are reported in Glaesner 2010.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/26089386/","title":"Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin Glargine in Patients With Type 2 Diabetes on Metformin and Glimepiride (AWARD-2)","publisher":"Diabetes Care (via PubMed)","date":"2015-12","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31189511/","title":"Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial","publisher":"The Lancet (via PubMed)","date":"2019-07-13","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35658022/","title":"Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes","publisher":"New England Journal of Medicine (via PubMed)","date":"2022-08-04","accessed":"2026-09-29"}],"label":"Approved"},"route":"Subcutaneous injection, once weekly, from a single-dose pen (approved use in type 2 diabetes).","halfLife":{"value":"About 5 days (elimination half-life)","source":{"url":"https://pi.lilly.com/us/trulicity-uspi.pdf","title":"TRULICITY (dulaglutide) injection, for subcutaneous use: full prescribing information","publisher":"Eli Lilly and Company (FDA-approved label)","date":"2026-03","accessed":"2026-09-29"}},"structure":{"pubchemCid":171042928,"pdb":[]},"companies":["eli-lilly"],"keyFacts":[{"label":"FDA approval","value":"Approved by the U.S. FDA on 2014-09-18 (BLA 125469) to Eli Lilly and Company.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/125469Orig1s000ltr.pdf","title":"BLA 125469/0 approval letter: Trulicity (dulaglutide)","publisher":"U.S. Food and Drug Administration","date":"2014-09-18","accessed":"2026-09-29"}},{"label":"EU authorisation","value":"European marketing authorisation issued on 2014-11-21 (EMEA/H/C/002825). It is now authorised for type 2 diabetes in adults and children from 10 years of age.","source":{"url":"https://www.ema.europa.eu/en/medicines/human/EPAR/trulicity","title":"Trulicity (dulaglutide): EPAR and product information","publisher":"European Medicines Agency","date":"2014-12","accessed":"2026-09-29"}},{"label":"Japan launch","value":"Launched in Japan on 2015-09-16 by Eli Lilly Japan and Sumitomo Dainippon Pharma after approval for type 2 diabetes; the company said approval had been gained in 45 countries and areas by then.","source":{"url":"https://www.sumitomo-pharma.com/news/20150916.html","title":"Market Release of Trulicity Subcutaneous Injection Ateos, Once-Weekly Type 2 Diabetes Treatment: GLP-1 Receptor Agonist","publisher":"Sumitomo Pharma","date":"2015-09-16","accessed":"2026-09-29"}},{"label":"REWIND cardiovascular result","value":"Primary outcome in 12.0% (594 of 4,949) on dulaglutide versus 13.4% (663 of 4,952) on placebo; hazard ratio 0.88 (95% CI 0.79-0.99).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/31189511/","title":"Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial","publisher":"The Lancet (via PubMed)","date":"2019-07-13","accessed":"2026-09-29"}},{"label":"Half-life and size","value":"Elimination half-life about 5 days; molecular weight about 63 kilodaltons.","source":{"url":"https://pi.lilly.com/us/trulicity-uspi.pdf","title":"TRULICITY (dulaglutide) injection, for subcutaneous use: full prescribing information","publisher":"Eli Lilly and Company (FDA-approved label)","date":"2026-03","accessed":"2026-09-29"}},{"label":"AWARD-PEDS (youths 10 to under 18)","value":"At 26 weeks HbA1c rose 0.6 percentage points on placebo and fell 0.6 and 0.9 points at the two studied doses; 51% of pooled dulaglutide participants reached HbA1c below 7.0% versus 14% on placebo.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/35658022/","title":"Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes","publisher":"New England Journal of Medicine (via PubMed)","date":"2022-08-04","accessed":"2026-09-29"}}],"safety":[{"text":"Boxed warning: dulaglutide causes thyroid C-cell tumours in rats. It is unknown whether it causes such tumours, including medullary thyroid carcinoma, in humans. It is contraindicated with a personal or family history of medullary thyroid carcinoma or in Multiple Endocrine Neoplasia syndrome type 2.","source":{"url":"https://pi.lilly.com/us/trulicity-uspi.pdf","title":"TRULICITY (dulaglutide) injection, for subcutaneous use: full prescribing information","publisher":"Eli Lilly and Company (FDA-approved label)","date":"2026-03","accessed":"2026-09-29"}},{"text":"Most common adverse reactions (5% or more) are nausea, diarrhoea, vomiting, abdominal pain and decreased appetite. In pooled placebo-controlled trials nausea occurred in 5.3% on placebo versus 12.4% and 21.1% at the two studied doses.","source":{"url":"https://pi.lilly.com/us/trulicity-uspi.pdf","title":"TRULICITY (dulaglutide) injection, for subcutaneous use: full prescribing information","publisher":"Eli Lilly and Company (FDA-approved label)","date":"2026-03","accessed":"2026-09-29"}},{"text":"In REWIND, 47.4% of participants on dulaglutide reported a gastrointestinal adverse event versus 34.1% on placebo.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/31189511/","title":"Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial","publisher":"The Lancet (via PubMed)","date":"2019-07-13","accessed":"2026-09-29"}},{"text":"Acute pancreatitis has been reported with GLP-1 receptor agonists including dulaglutide; the label says to discontinue if pancreatitis is suspected. Use with insulin or an insulin secretagogue may raise the risk of hypoglycaemia.","source":{"url":"https://pi.lilly.com/us/trulicity-uspi.pdf","title":"TRULICITY (dulaglutide) injection, for subcutaneous use: full prescribing information","publisher":"Eli Lilly and Company (FDA-approved label)","date":"2026-03","accessed":"2026-09-29"}},{"text":"Other label warnings include serious hypersensitivity reactions, acute kidney injury from volume depletion, gallbladder disease, diabetic retinopathy complications, pulmonary aspiration during anaesthesia or deep sedation, and severe gastrointestinal adverse reactions (listed as a recent major label change in 03/2026; not recommended in severe gastroparesis).","source":{"url":"https://pi.lilly.com/us/trulicity-uspi.pdf","title":"TRULICITY (dulaglutide) injection, for subcutaneous use: full prescribing information","publisher":"Eli Lilly and Company (FDA-approved label)","date":"2026-03","accessed":"2026-09-29"}}],"related":["semaglutide","liraglutide","exenatide","tirzepatide"],"lastVerified":"2026-09-29"},{"slug":"ecnoglutide","name":"Ecnoglutide","url":"https://glp1base.com/molecules/ecnoglutide","aliases":["XW003","XW-003","Ecnoglutide injection"],"brands":[{"name":"Xianyida (先颐达)","company":"sciwind-biosciences","indication":"Once-weekly injection for glycaemic control in adults with type 2 diabetes in mainland China; NMPA approval announced by Sciwind on 2026-01-30; commercialised in mainland China by Pfizer China"},{"name":"Xianweiying (先维盈)","company":"sciwind-biosciences","indication":"Once-weekly injection for long-term weight management, alongside diet and physical activity, in adults with overweight or obesity in mainland China; NMPA approval announced by Sciwind on 2026-03-06; commercialised in mainland China by Pfizer China"}],"class":"glp1-approved","classLabel":"Approved GLP-1 medicine","targets":["GLP-1 receptor"],"summarySimple":"Ecnoglutide is a once-a-week injection that copies a gut hormone called GLP-1. It helps the body release insulin and makes people feel full. China approved it in 2026 for type 2 diabetes and for weight management. No approval from the US, EU or UK regulators was found as of late September 2026.","summaryExpert":"Ecnoglutide (XW003) is a once-weekly, subcutaneously administered, acylated 31-residue analogue of GLP-1(7-37), developed by Hangzhou Sciwind Biosciences (PubChem CID 162625103; C194H304N48O61, about 4,285 Da). Relative to native GLP-1(7-37) it carries Ala8Val, Gly22Glu, Lys26Arg, Ala30Lys and Lys34Arg substitutions, and a C18 diacid fatty acid attached through a gamma-Glu-2xAEEA linker to Lys30, which promotes albumin binding and extends half-life; it contains only natural amino acids. In vitro it activates cAMP signalling with an EC50 of 0.018 nM, while beta-arrestin recruitment reaches about 60% of the semaglutide maximum and receptor internalisation is much weaker than with semaglutide (EC50 above 10 uM versus 0.093 uM); the sponsor calls this a cAMP-biased profile, and its clinical significance relative to unbiased agonists has not been shown in a head-to-head human trial. In a phase 1 study in healthy adults (n=64), steady-state half-life was 124 to 138 hours. Sciwind announced China NMPA approval for glycaemic control in adults with type 2 diabetes on 2026-01-30 (brand Xianyida) and for long-term weight management in adults with overweight or obesity on 2026-03-06 (brand Xianweiying). Key phase 3 trials: SLIMMER (NCT05813795; 664 adults with overweight or obesity, placebo-controlled, weight change at week 40 of -9.1%, -10.9% and -13.2% across the three tested doses versus +0.1% on placebo); EECOH-1 (NCT05680155; HbA1c change of -1.96% and -2.43% versus -0.87% on placebo at week 24); and EECOH-2 (NCT05680129; non-inferior to dulaglutide at the comparator dose, HbA1c -1.91% and -1.89% versus -1.65% at week 32). All pivotal trials were run in Chinese adults. Pfizer China holds mainland-China commercial rights, with Sciwind as marketing authorisation holder. Regulatory approval outside China was not found as of 2026-09-29.","evidence":{"level":"approved","note":"Approved by China's NMPA (approvals announced by the sponsor on 2026-01-30 for type 2 diabetes and 2026-03-06 for weight management), which is a major regulator on the schema's list. The approvals rest on three randomised phase 3 trials in Chinese adults, published in peer-reviewed journals: SLIMMER (obesity, placebo-controlled, 48 weeks), EECOH-1 (type 2 diabetes, placebo-controlled, 24 weeks) and EECOH-2 (type 2 diabetes versus dulaglutide, 52 weeks). A phase 2 diabetes trial and a phase 1 study in healthy adults preceded them. No approval from the FDA, EMA, MHRA, PMDA, TGA or Health Canada was found. All the pivotal trials were sponsor-funded and done only in China, so results may not transfer to other populations. Further phase 3 studies (obstructive sleep apnoea and knee osteoarthritis in adults with obesity) are registered and recruiting, and a phase 3 study in adolescents with overweight or obesity (SLIMMER-YOUNG) is registered but not yet recruiting; those uses are investigational and not approved.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/40555243/","title":"Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (SLIMMER)","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2025-09","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41501026/","title":"Efficacy and safety of cAMP signalling-biased GLP-1 analogue ecnoglutide monotherapy versus placebo in patients with type 2 diabetes (EECOH-1): a multi-centre, randomised, double-blind, placebo-controlled, phase 3 trial","publisher":"Nature Communications (PubMed)","date":"2026-01-07","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40854315/","title":"Efficacy and safety of cAMP-biased GLP-1 receptor agonist ecnoglutide versus dulaglutide in patients with type 2 diabetes and elevated glucose concentrations on metformin monotherapy (EECOH-2): a 52-week, multicentre, open-label, non-inferiority, randomised, phase 3 trial","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2025-10","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39333121/","title":"Efficacy and safety of GLP-1 analog ecnoglutide in adults with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial","publisher":"Nature Communications (PubMed)","date":"2024-09-27","accessed":"2026-09-29"},{"url":"https://www.prnewswire.com/news-releases/sciwind-biosciences-announces-ecnoglutide-injection-approved-by-chinas-national-medical-products-administration-nmpa-for-chronic-weight-management-302706442.html","title":"Sciwind Biosciences Announces Ecnoglutide Injection Approved by China's National Medical Products Administration (NMPA) for Chronic Weight Management","publisher":"Sciwind Biosciences (PR Newswire)","date":"2026-03-06","accessed":"2026-09-29"},{"url":"https://www.prnewswire.com/apac/news-releases/sciwind-biosciences-announces-ecnoglutide-injection-approved-by-chinas-national-medical-products-administration-nmpa-for-adult-type-2-diabetes-302675016.html","title":"Sciwind Biosciences Announces Ecnoglutide Injection Approved by China's National Medical Products Administration (NMPA) for Adult Type 2 Diabetes","publisher":"Sciwind Biosciences (PR Newswire)","date":"2026-01-30","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT07434050","title":"A Study of XW003 in Obese Participants With Obstructive Sleep Apnea Receiving Positive Airway Pressure Therapy, NCT07434050","publisher":"ClinicalTrials.gov","date":"2026-02-25","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT07734311","title":"A Study of Econoglutide Injection in Obese Participants With Knee Osteoarthritis (KOA), NCT07734311","publisher":"ClinicalTrials.gov","date":"2026-07-29","accessed":"2026-09-29"},{"url":"https://www.sciwind.com.cn/portal/index/newsdetail/id/131.html","title":"全球首个偏向型GLP-1埃诺格鲁肽注射液获批！ (Xianyida approved for type 2 diabetes)","publisher":"Hangzhou Sciwind Biosciences","date":"2026-01-30","accessed":"2026-09-29"},{"url":"https://www.sciwind.com.cn/portal/index/newsdetail/id/135.html","title":"全球首个偏向型GLP-1减重药物先维盈®获批上市！ (Xianweiying approved for weight management)","publisher":"Hangzhou Sciwind Biosciences","date":"2026-03-06","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT07836270","title":"A Study of Ecnoglutide Injection in Overweight or Obese Chinese Adolescents (SLIMMER-YOUNG), NCT07836270","publisher":"ClinicalTrials.gov","date":"2026-09-23","accessed":"2026-09-29"}],"label":"Approved"},"route":"Subcutaneous injection, given once weekly (as studied in the phase 3 trials and approved in China). Oral tablet versions are being studied separately and are investigational.","halfLife":{"value":"Steady-state half-life of about 124 to 138 hours (roughly 5 to 6 days) in healthy adults in the phase 1 multiple-dose study, supporting once-weekly injection","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/37364710/","title":"Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog","publisher":"Molecular Metabolism (PubMed)","date":"2023-09","accessed":"2026-09-29"}},"structure":{"pubchemCid":162625103,"pdb":[{"id":"6X18","description":"Cryo-EM structure (2.1 A, released 2020-09-09) of the human GLP-1 receptor bound to native GLP-1(7-36)NH2 and a Gs protein complex (with a nanobody). It shows how the natural hormone that ecnoglutide imitates fits its receptor; it does not contain ecnoglutide itself."}]},"companies":["sciwind-biosciences","pfizer"],"keyFacts":[{"label":"China approval: type 2 diabetes","value":"Sciwind announced on 2026-01-30 that China's NMPA had approved ecnoglutide for glycaemic control in adults with type 2 diabetes.","source":{"url":"https://www.prnewswire.com/apac/news-releases/sciwind-biosciences-announces-ecnoglutide-injection-approved-by-chinas-national-medical-products-administration-nmpa-for-adult-type-2-diabetes-302675016.html","title":"Sciwind Biosciences Announces Ecnoglutide Injection Approved by China's National Medical Products Administration (NMPA) for Adult Type 2 Diabetes","publisher":"Sciwind Biosciences (PR Newswire)","date":"2026-01-30","accessed":"2026-09-29"}},{"label":"China approval: weight management","value":"Sciwind announced on 2026-03-06 that China's NMPA had approved ecnoglutide for chronic weight management in adults with overweight or obesity.","source":{"url":"https://www.prnewswire.com/news-releases/sciwind-biosciences-announces-ecnoglutide-injection-approved-by-chinas-national-medical-products-administration-nmpa-for-chronic-weight-management-302706442.html","title":"Sciwind Biosciences Announces Ecnoglutide Injection Approved by China's National Medical Products Administration (NMPA) for Chronic Weight Management","publisher":"Sciwind Biosciences (PR Newswire)","date":"2026-03-06","accessed":"2026-09-29"}},{"label":"Commercial partner","value":"Pfizer holds exclusive commercialisation rights in mainland China (announced February 2026); Sciwind remains marketing authorisation holder and is eligible for up to $495 million in upfront, regulatory and sales milestone payments.","source":{"url":"https://www.sec.gov/Archives/edgar/data/0000078003/000007800326000095/pfe-20260628.htm","title":"Pfizer Inc. Form 10-Q for the quarterly period ended June 28, 2026 (In-Licensing Arrangement with Sciwind Biosciences)","publisher":"U.S. Securities and Exchange Commission (Pfizer Inc.)","date":"2026-08-04","accessed":"2026-09-29"}},{"label":"SLIMMER phase 3 result (week 40)","value":"Mean body-weight change of -9.1%, -10.9% and -13.2% across the three tested doses versus +0.1% on placebo (664 adults; treatment differences -9.2%, -11.1%, -13.3%).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40555243/","title":"Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (SLIMMER)","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2025-09","accessed":"2026-09-29"}},{"label":"EECOH-2 versus dulaglutide (week 32)","value":"HbA1c fell 1.91% and 1.89% with the two ecnoglutide doses versus 1.65% with dulaglutide at the comparator dose; both doses met non-inferiority, and the authors judged the difference for the higher dose not clinically relevant.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40854315/","title":"Efficacy and safety of cAMP-biased GLP-1 receptor agonist ecnoglutide versus dulaglutide in patients with type 2 diabetes and elevated glucose concentrations on metformin monotherapy (EECOH-2): a 52-week, multicentre, open-label, non-inferiority, randomised, phase 3 trial","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2025-10","accessed":"2026-09-29"}},{"label":"Half-life","value":"Mean steady-state half-life of 124 to 138 hours across the multiple-dose cohorts in healthy adults (phase 1), supporting once-weekly use.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/37364710/","title":"Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog","publisher":"Molecular Metabolism (PubMed)","date":"2023-09","accessed":"2026-09-29"}}],"safety":[{"text":"In the 48-week SLIMMER obesity trial, treatment-emergent adverse events occurred in 93% of participants on each ecnoglutide dose versus 84% on placebo. The most common were mild-to-moderate gastrointestinal events, and 10 ecnoglutide participants stopped treatment because of adverse events.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40555243/","title":"Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (SLIMMER)","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2025-09","accessed":"2026-09-29"}},{"text":"In the 52-week EECOH-2 trial versus dulaglutide, treatment stopped because of adverse events in 3% (6 of 206) and 4% (8 of 208) of participants on the two ecnoglutide doses and 3% (6 of 207) on dulaglutide.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40854315/","title":"Efficacy and safety of cAMP-biased GLP-1 receptor agonist ecnoglutide versus dulaglutide in patients with type 2 diabetes and elevated glucose concentrations on metformin monotherapy (EECOH-2): a 52-week, multicentre, open-label, non-inferiority, randomised, phase 3 trial","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2025-10","accessed":"2026-09-29"}},{"text":"In the phase 1 study in healthy adults, reported adverse events included decreased appetite, nausea and headache.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/37364710/","title":"Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog","publisher":"Molecular Metabolism (PubMed)","date":"2023-09","accessed":"2026-09-29"}},{"text":"The pivotal trials were sponsor-funded, done only in Chinese adults, and lasted 24 to 52 weeks; long-term safety and safety in other populations are not established by these trials.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40555243/","title":"Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (SLIMMER)","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2025-09","accessed":"2026-09-29"}},{"text":"Other uses, such as obstructive sleep apnoea in adults with obesity, are being studied in registered trials and are not approved.","source":{"url":"https://clinicaltrials.gov/study/NCT07434050","title":"A Study of XW003 in Obese Participants With Obstructive Sleep Apnea Receiving Positive Airway Pressure Therapy, NCT07434050","publisher":"ClinicalTrials.gov","date":"2026-02-25","accessed":"2026-09-29"}}],"related":["semaglutide","dulaglutide","liraglutide","tirzepatide","mazdutide"],"lastVerified":"2026-09-29"},{"slug":"elamipretide","name":"Elamipretide (SS-31)","url":"https://glp1base.com/molecules/elamipretide","aliases":["SS-31","Bendavia","MTP-131","Szeto-Schiller peptide 31","D-Arg-Dmt-Lys-Phe-NH2","Elamipretide hydrochloride"],"brands":[{"name":"Forzinity","company":"stealth-biotherapeutics","indication":"To improve muscle strength in adults and children with Barth syndrome weighing at least 30 kg (US, accelerated approval)"}],"class":"peptide-approved","classLabel":"Approved peptide medicine","targets":["Cardiolipin, a fat molecule in the inner mitochondrial membrane (the peptide binds it)","Cardiolipin-binding proteins of the mitochondrial energy machinery, such as ATP synthase and the adenine nucleotide translocator (identified in mouse-heart mitochondria)"],"summarySimple":"Elamipretide is a tiny four-piece protein that gets inside cells and sticks to the inner wall of mitochondria, the parts that make energy. In September 2025 the US FDA gave it a conditional (accelerated) approval for Barth syndrome, a rare genetic muscle and heart disease. Its other tried uses are not approved.","summaryExpert":"Elamipretide (SS-31, MTP-131, Bendavia) is a synthetic tetrapeptide, D-Arg-2',6'-dimethyl-Tyr-Lys-Phe-NH2, a Szeto-Schiller peptide (C32H49N9O5, 639.8 Da as the free base; the marketed hydrochloride salt is 749.2). The alternating basic and aromatic residues make it polybasic and amphipathic. The D-arginine and the non-natural dimethyltyrosine are the engineered features: dimethyltyrosine gives antioxidant properties in vitro. It is cell-permeable and concentrates in the inner mitochondrial membrane (IMM) in cell and isolated-mitochondria work. It binds the anionic phospholipid cardiolipin, alters membrane surface electrostatics and protein-lipid interactions, and, in isolated mouse-heart mitochondria, cross-links to cardiolipin-binding proteins of oxidative phosphorylation (ATP synthase, respiratory complexes III and IV, the adenine nucleotide translocator); in rodent ischaemia-reperfusion models it preserves cristae structure and ATP recovery. The FDA label calls it a mitochondrial cardiolipin binder. Pharmacokinetics (FDA label and review): after subcutaneous injection the absolute bioavailability is about 92%, Tmax 0.5-1 h, volume of distribution about 0.5 L/kg, plasma protein binding about 39%; it is cleared by C-terminal degradation to inactive tri- and dipeptide metabolites, with about 100% of a dose recovered in urine within 48 h, and a half-life of about 3-4 h; exposure rises in renal impairment. Barth syndrome is an X-linked disorder of TAFAZZIN (TAZ), the enzyme that matures cardiolipin. The FDA granted accelerated approval on 19 September 2025 (Forzinity, NDA 215244) to improve muscle strength in patients with Barth syndrome weighing at least 30 kg, based on knee-extensor strength (an intermediate endpoint) in the TAZPOWER trial: a 12-patient randomised crossover trial that missed both primary endpoints, followed by an open-label extension with no control arm in which strength rose. FDA reviewers were divided on whether this was substantial evidence. Continued approval depends on a confirmatory trial. The phase 3 MMPOWER-3 trial in primary mitochondrial myopathy missed its primary endpoints, phase 2 trials in heart failure and heart attack did not meet their main endpoints, and the phase 2 ReCLAIM-2 trial in dry AMD missed its primary endpoints; a phase 3 dry AMD trial (ReNEW) is ongoing. These other uses are unapproved. No approval outside the US was found; the sponsor reports an EU orphan designation for Barth syndrome, which is a rare-disease development status, not an approval.","evidence":{"level":"approved","note":"Approved only in the US, under accelerated approval (19 September 2025), for Barth syndrome. The pivotal package is very small: TAZPOWER randomised 12 people; in the randomised part neither primary endpoint (6-minute walk, fatigue score) beat placebo, and knee strength rose only in the open-label extension, which had no control group. FDA reviewers disagreed on whether this was enough. In other conditions, the phase 3 MMPOWER-3 trial (primary mitochondrial myopathy, 218 people) missed its primary endpoints, phase 2 trials in heart failure and heart attack did not meet their main endpoints, and the phase 2 dry-AMD trial ReCLAIM-2 missed its primary endpoints (a phase 3, ReNEW, is running). Those uses are not approved.","sources":[{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/215244Orig1s000IntegratedR.pdf","title":"NDA 215244 Forzinity (elamipretide) Integrated Review","publisher":"U.S. Food and Drug Administration (CDER)","date":"2025-09-19","accessed":"2026-09-29"},{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf","title":"FORZINITY (elamipretide) injection, prescribing information (FDA label, NDA 215244)","publisher":"U.S. Food and Drug Administration (Drugs@FDA)","date":"2025-09","accessed":"2026-09-29"},{"url":"https://doi.org/10.1016/j.gim.2024.101138","title":"Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER","publisher":"Genetics in Medicine","date":"2024-07","accessed":"2026-09-29"},{"url":"https://doi.org/10.1212/WNL.0000000000207402","title":"Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial","publisher":"Neurology","date":"2023-07","accessed":"2026-09-29"},{"url":"https://doi.org/10.1016/j.xops.2024.100628","title":"ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation","publisher":"Ophthalmology Science","date":"2024-10","accessed":"2026-09-29"}],"label":"Approved"},"route":"Given by subcutaneous injection in its approved use (US label); it is not approved for intravenous use. In research it has also been given by intravenous infusion (for example, the EMBRACE STEMI heart-attack trial and a single-dose study in older adults); that route is not approved.","halfLife":{"value":"About 3 to 4 hours (FDA review). After a single subcutaneous dose the mean half-life was 3.16 h in healthy volunteers and 1.48 h in people with Barth syndrome.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/215244Orig1s000IntegratedR.pdf","title":"NDA 215244 Forzinity (elamipretide) Integrated Review","publisher":"U.S. Food and Drug Administration (CDER)","date":"2025-09-19","accessed":"2026-09-29"}},"structure":{"pubchemCid":11764719,"pdb":[]},"companies":["stealth-biotherapeutics"],"keyFacts":[{"label":"US approval","value":"Accelerated approval by the FDA on 19 September 2025 (Forzinity, NDA 215244) to improve muscle strength in patients with Barth syndrome weighing at least 30 kg; the company describes it as the first FDA-approved mitochondria-targeted therapeutic. Continued approval may depend on a confirmatory trial.","source":{"url":"https://www.prnewswire.com/news-releases/stealth-biotherapeutics-announces-fda-accelerated-approval-of-forzinity-elamipretide-hcl-the-first-therapy-for-progressive-and-life-limiting-ultra-rare-genetic-disease-barth-syndrome-302562058.html","title":"Stealth BioTherapeutics Announces FDA Accelerated Approval of FORZINITY (elamipretide HCl), the First Therapy for Progressive and Life-limiting Ultra-rare Genetic Disease Barth Syndrome","publisher":"Stealth BioTherapeutics (PR Newswire)","date":"2025-09-19","accessed":"2026-09-29"}},{"label":"Pivotal trial (TAZPOWER)","value":"12 males with genetically confirmed Barth syndrome; in the randomised part the drug was not superior to placebo on either primary endpoint (6-minute walk, fatigue score).","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf","title":"FORZINITY (elamipretide) injection, prescribing information (FDA label, NDA 215244)","publisher":"U.S. Food and Drug Administration (Drugs@FDA)","date":"2025-09","accessed":"2026-09-29"}},{"label":"Knee muscle strength, open-label extension","value":"Baseline median 124 newtons; median change from baseline +63 N at week 168 in the 8 patients who reached that visit. During the randomised part, week-12 change was +4 N on drug vs -5 N on placebo.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf","title":"FORZINITY (elamipretide) injection, prescribing information (FDA label, NDA 215244)","publisher":"U.S. Food and Drug Administration (Drugs@FDA)","date":"2025-09","accessed":"2026-09-29"}},{"label":"Primary mitochondrial myopathy (phase 3, unapproved use)","value":"MMPOWER-3, 218 participants: the difference from placebo in 6-minute walk distance at week 24 was -3.2 m (95% CI -18.7 to 12.3; p=0.69); primary endpoints not met.","source":{"url":"https://doi.org/10.1212/WNL.0000000000207402","title":"Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial","publisher":"Neurology","date":"2023-07","accessed":"2026-09-29"}},{"label":"Dry AMD (phase 2, unapproved use)","value":"ReCLAIM-2, 176 patients: primary endpoints not met; 43% less progression of total ellipsoid-zone loss vs placebo at week 48 (nominal P=0.0034).","source":{"url":"https://doi.org/10.1016/j.xops.2024.100628","title":"ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation","publisher":"Ophthalmology Science","date":"2024-10","accessed":"2026-09-29"}},{"label":"Molecular weight","value":"639.8 Da (free base, C32H49N9O5); the hydrochloride salt used in the product is 749.2.","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/11764719","title":"Elamipretide (CID 11764719)","publisher":"PubChem, National Center for Biotechnology Information","date":"2006-10-26","accessed":"2026-09-29"}}],"safety":[{"text":"Injection-site reactions were the most common adverse reactions. In the placebo-controlled crossover study, any local reaction occurred in 12 of 12 people on elamipretide versus 8 of 12 on placebo (injection-site redness 100% vs 25%, pain 75% vs 42%, hardening 67% vs 17%).","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf","title":"FORZINITY (elamipretide) injection, prescribing information (FDA label, NDA 215244)","publisher":"U.S. Food and Drug Administration (Drugs@FDA)","date":"2025-09","accessed":"2026-09-29"}},{"text":"Hypersensitivity reactions, including serious allergic reactions needing emergency treatment, have been reported, with skin and respiratory features; they can appear from minutes to months after starting. Serious hypersensitivity to the drug or its ingredients is a contraindication.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf","title":"FORZINITY (elamipretide) injection, prescribing information (FDA label, NDA 215244)","publisher":"U.S. Food and Drug Administration (Drugs@FDA)","date":"2025-09","accessed":"2026-09-29"}},{"text":"The product contains the preservative benzyl alcohol. It is not approved for newborns; serious and fatal toxicity (gasping syndrome) has been reported in low-birth-weight and preterm neonates given benzyl-alcohol-containing drugs intravenously.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf","title":"FORZINITY (elamipretide) injection, prescribing information (FDA label, NDA 215244)","publisher":"U.S. Food and Drug Administration (Drugs@FDA)","date":"2025-09","accessed":"2026-09-29"}},{"text":"Blood eosinophil counts often rose with treatment of 30 days or longer (peak around 90 days, mean rise about 0.5-0.6 x10^3/uL), returning to baseline after 6-12 months of continued use or after stopping. The rise was not linked to clinical problems or other lab changes in the label data.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf","title":"FORZINITY (elamipretide) injection, prescribing information (FDA label, NDA 215244)","publisher":"U.S. Food and Drug Administration (Drugs@FDA)","date":"2025-09","accessed":"2026-09-29"}},{"text":"The safety database in Barth syndrome is very small (12 patients in the clinical program, all male, aged 12 to 35), so uncommon risks may not have been seen. Use in people over 65 and in dialysis-dependent kidney failure has not been studied.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf","title":"FORZINITY (elamipretide) injection, prescribing information (FDA label, NDA 215244)","publisher":"U.S. Food and Drug Administration (Drugs@FDA)","date":"2025-09","accessed":"2026-09-29"}},{"text":"Kidney function changes exposure: drug levels (AUC) were 125% higher in severe renal impairment not on dialysis, and levels of its inactive breakdown products were much higher (up to 280% and 640%).","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf","title":"FORZINITY (elamipretide) injection, prescribing information (FDA label, NDA 215244)","publisher":"U.S. Food and Drug Administration (Drugs@FDA)","date":"2025-09","accessed":"2026-09-29"}}],"related":["mots-c"],"lastVerified":"2026-09-29"},{"slug":"eloralintide","name":"Eloralintide","url":"https://glp1base.com/molecules/eloralintide","aliases":["LY3841136","LY-3841136"],"brands":[],"class":"amylin","classLabel":"Amylin analogue","targets":["Amylin 1 receptor (AMY1R: calcitonin receptor with RAMP1)","Amylin 3 receptor (AMY3R: calcitonin receptor with RAMP3)"],"summarySimple":"Eloralintide is an experimental once-weekly injection being tested for obesity. It copies amylin, a hormone made in the pancreas after meals that helps you feel full. It is not a GLP-1 drug. In a 48-week trial of 263 adults, average weight loss ranged from 9.5% to 20.1%, versus 0.4% on placebo. It is not approved anywhere yet.","summaryExpert":"Eloralintide (LY3841136, Eli Lilly) is a synthetic, C-terminally amidated 37-residue analogue of human amylin, designed as a selective amylin receptor agonist for once-weekly subcutaneous use. Engineering features: the native Cys2-Cys7 disulfide is replaced by a methylene thioacetal bridge (chemical stability); three non-coded residues (ornithine at position 11, alpha-methyl-phenylalanine at 15, N-methyl-asparagine at 22); an N-terminal gamma-glutamate; and Lys26 acylated through a gamma-Glu-gamma-Glu linker with a C20 fatty diacid to bind albumin and extend half-life. In cAMP assays it was about 12-fold more potent at human AMY1R (EC50 23.9 pM) than at the human calcitonin receptor and about 11-fold more potent than at AMY3R, unlike the non-selective dual amylin/calcitonin agonist cagrilintide. Pharmacokinetics in people with obesity: slow absorption, half-life about 14 days, dose-proportional exposure and low steady-state peak-to-trough ratios (1.28 to 1.38). Key human data: a phase 1 single-ascending-dose study in healthy adults (NCT05295940), a 12-week phase 1 multiple-ascending-dose study (100 participants; least-squares mean weight reduction 2.6% to 11.3% across dose groups), and a 48-week phase 2 trial (NCT06230523; 263 adults without type 2 diabetes; mean weight change -9% to -20% across arms versus -0.4% on placebo, efficacy estimand; most common adverse events nausea and fatigue). Phase 3 (ENLIGHTEN) began in December 2025 and is recruiting; no phase 3 efficacy results are public as of 2026-09-29. It has no marketing approval from any regulator, and Lilly describes it as investigational.","evidence":{"level":"phase3","note":"Phase 3 (ENLIGHTEN programme) is registered and recruiting; the first phase 3 trial (ENLIGHTEN-2, NCT07282600) started on 2025-12-15, and no phase 3 results are public as of 2026-09-29. The strongest completed human evidence is a 48-week randomised, double-blind, placebo-controlled phase 2 trial in 263 adults with obesity or overweight and no type 2 diabetes (Lancet 2025), supported by phase 1 single- and multiple-ascending-dose studies. Receptor pharmacology, pharmacokinetics in rats and monkeys, and body-composition data come from cell and animal studies. The phase 2 trial was funded by Lilly, and Lilly's summary notes that its endpoints were assessed with the efficacy estimand and not adjusted for multiplicity.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/41207310/","title":"Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial","publisher":"The Lancet (via PubMed)","date":"2025-11-06","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT07321886","title":"A Study of Eloralintide (LY3841136) in Participants With Obesity, or Overweight Without Type 2 Diabetes (ENLIGHTEN-1 phase 3 record)","publisher":"ClinicalTrials.gov (U.S. National Library of Medicine)","date":"2026-09-22","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT07282600","title":"A Study of Eloralintide (LY3841136) in Participants With Obesity or Overweight, and Type 2 Diabetes (ENLIGHTEN-2 phase 3 record)","publisher":"ClinicalTrials.gov (U.S. National Library of Medicine)","date":"2026-09-22","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41559929/","title":"Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept","publisher":"Diabetes, Obesity and Metabolism (via PubMed)","date":"2026-01-20","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41109426/","title":"Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept","publisher":"Molecular Metabolism (via PubMed)","date":"2025-10-16","accessed":"2026-09-29"}],"label":"Phase 3 trials"},"route":"Subcutaneous injection, once weekly, in clinical trials (investigational; not an approved medicine, so there is no approved route of use).","halfLife":{"value":"About 14 days (people with obesity or overweight, reported in the phase 1 multiple-ascending-dose paper)","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/41559929/","title":"Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept","publisher":"Diabetes, Obesity and Metabolism (via PubMed)","date":"2026-01-20","accessed":"2026-09-29"}},"structure":{"pubchemCid":175663130,"pdb":[]},"companies":["eli-lilly"],"keyFacts":[{"label":"Regulatory status","value":"Investigational. Lilly states it is not approved by the FDA, and no marketing approval from any regulator was found as of 2026-09-29. Any submission depends on the results of ongoing and future trials.","source":{"url":"https://www.lilly.com/news/stories/what-to-know-about-eloralintide","title":"What to know about eloralintide","publisher":"Eli Lilly and Company","date":"2025-11","accessed":"2026-09-29"}},{"label":"Phase 2 weight change (48 weeks)","value":"Mean change from -9.5% to -20.1% across six eloralintide arms versus -0.4% with placebo (efficacy estimand; 263 adults with obesity or overweight, no type 2 diabetes; company-funded).","source":{"url":"https://www.prnewswire.com/news-releases/lillys-selective-amylin-agonist-eloralintide-demonstrated-meaningful-weight-loss-and-favorable-tolerability-in-a-phase-2-study-of-adults-with-obesity-or-overweight-302607061.html","title":"Lilly's selective amylin agonist, eloralintide, demonstrated meaningful weight loss and favorable tolerability in a Phase 2 study of adults with obesity or overweight","publisher":"Eli Lilly and Company (press release)","date":"2025-11-06","accessed":"2026-09-29"}},{"label":"Phase 3 programme","value":"ENLIGHTEN-1 (NCT07321886), a placebo-controlled phase 3 trial in adults with obesity or overweight without type 2 diabetes, started 2026-02-06 with about 1,980 participants planned; status recruiting, record last updated 2026-09-22. No results yet.","source":{"url":"https://clinicaltrials.gov/study/NCT07321886","title":"A Study of Eloralintide (LY3841136) in Participants With Obesity, or Overweight Without Type 2 Diabetes","publisher":"ClinicalTrials.gov (U.S. National Library of Medicine)","date":"2026-09-22","accessed":"2026-09-29"}},{"label":"Half-life","value":"About 14 days in people with obesity or overweight, with slow absorption and steady-state peak-to-trough ratios of 1.28 to 1.38.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/41559929/","title":"Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept","publisher":"Diabetes, Obesity and Metabolism (via PubMed)","date":"2026-01-20","accessed":"2026-09-29"}},{"label":"Receptor selectivity (cell assays)","value":"About 12-fold more potent at human AMY1R (EC50 23.9 pM) than at the human calcitonin receptor, and about 11-fold more potent than at AMY3R. Cell-line data, not a clinical result.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/41109426/","title":"Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept","publisher":"Molecular Metabolism (via PubMed)","date":"2025-10-16","accessed":"2026-09-29"}},{"label":"Molecular weight and formula","value":"About 4,526 g/mol; C201H319N49O65S2 (37-residue lipidated peptide).","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/175663130","title":"Eloralintide (PubChem CID 175663130)","publisher":"PubChem (U.S. National Library of Medicine)","date":"2026","accessed":"2026-09-29"}}],"safety":[{"text":"Phase 2 (48 weeks): the most common adverse events were nausea (11% to 64% across eloralintide arms versus 14% on placebo) and fatigue (0% to 46% versus 12%). Rates did not rise in a straight line with dose across the six arms.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/41207310/","title":"Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial","publisher":"The Lancet (via PubMed)","date":"2025-11-06","accessed":"2026-09-29"}},{"text":"Lilly reports the phase 2 adverse events were mostly mild to moderate gastrointestinal symptoms and fatigue, seen more often in higher-dose arms, less often with slower dose escalation, and similar to placebo in the two lowest-dose arms.","source":{"url":"https://www.prnewswire.com/news-releases/lillys-selective-amylin-agonist-eloralintide-demonstrated-meaningful-weight-loss-and-favorable-tolerability-in-a-phase-2-study-of-adults-with-obesity-or-overweight-302607061.html","title":"Lilly's selective amylin agonist, eloralintide, demonstrated meaningful weight loss and favorable tolerability in a Phase 2 study of adults with obesity or overweight","publisher":"Eli Lilly and Company (press release)","date":"2025-11-06","accessed":"2026-09-29"}},{"text":"Phase 1 multiple-ascending-dose study (12 weeks, 100 participants): most common adverse events were decreased appetite (19%), headache (12%), fatigue (11%) and COVID-19 (11%); diarrhoea 10%, nausea 8% and vomiting 4%. Most events were mild. There were no deaths and one serious adverse event judged unrelated to the drug.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/41559929/","title":"Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept","publisher":"Diabetes, Obesity and Metabolism (via PubMed)","date":"2026-01-20","accessed":"2026-09-29"}},{"text":"Phase 1 single-ascending-dose study in 48 healthy adults: 16 adverse events in 9 eloralintide recipients, 15 of them mild; four gastrointestinal events in two participants, including one moderate vomiting event.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/41109426/","title":"Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept","publisher":"Molecular Metabolism (via PubMed)","date":"2025-10-16","accessed":"2026-09-29"}},{"text":"Eloralintide is investigational. Lilly says it is still running clinical trials of its safety and efficacy, and that any regulatory submission depends on the outcomes of ongoing and future trials. Its long-term safety profile is therefore not established.","source":{"url":"https://www.lilly.com/news/stories/what-to-know-about-eloralintide","title":"What to know about eloralintide","publisher":"Eli Lilly and Company","date":"2025-11","accessed":"2026-09-29"}}],"related":["pramlintide","cagrilintide","amycretin","tirzepatide"],"lastVerified":"2026-09-29"},{"slug":"epitalon","name":"Epitalon","url":"https://glp1base.com/molecules/epitalon","aliases":["Epithalon","Epitalone","AEDG peptide","Ala-Glu-Asp-Gly","Tetrapeptide AEDG","AE-0 peptide"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["No confirmed molecular target (laboratory studies report effects on telomerase expression, melatonin and circadian-clock gene expression, and gene regulation)"],"summarySimple":"Epitalon is a tiny lab-made chain of four amino acids (building blocks of proteins), copied from the make-up of an extract from cow pineal glands. It is not an approved medicine in the US, and we found no approval by any other regulator. Most of the research comes from one Russian group, in cells and animals, with a few small human studies. It has never been tested for safety in a proper trial.","summaryExpert":"Epitalon (epithalon, AEDG) is a synthetic linear tetrapeptide, L-Ala-L-Glu-L-Asp-Gly (C14H22N4O9, 390.35 g/mol), designed by V. Khavinson's group at the St Petersburg Institute of Bioregulation and Gerontology from the amino-acid composition of epithalamin, a polypeptide extract of bovine pineal gland; FDA treats epitalon and epithalamin as different substances. It is unmodified: no D-amino acids, lipidation or other half-life engineering. Epitalon is a common name, not a USAN, and the free base (CAS 307297-39-8) and the acetate salt (CAS 307297-40-1) are distinct bulk substances. Reported effects, mostly from the originating group, include induction of telomerase catalytic-subunit expression and telomere elongation in cultured human fetal fibroblasts, increased evening melatonin and normalised cortisol rhythm in old rhesus monkeys, fewer or smaller spontaneous tumours of some types in some mouse models, and altered gene expression in several tissues. An in-vitro rat pineal perifusion study found no direct effect on melatonin release, and the mechanism in vivo is unknown. Human evidence is limited to three small reports identified by FDA: a report of benefit in retinitis pigmentosa after injection beside the eye, and two 2021 reports of sublingual use in women working night shifts, one of them a small randomised placebo-controlled study that measured a urinary melatonin metabolite and clock-gene expression. No pharmacokinetic data exist in humans or, apart from one unvalidated fluorescence-tracer report in rabbits, in animals. No approved product contains epitalon and there is no USP or NF monograph. An orphan designation for retinitis pigmentosa (FDA, 2010) was withdrawn in 2016. FDA staff recommended in 2026 against adding it to the 503A bulks list, citing weak characterisation, no effectiveness data for insomnia and no human safety data, and flagging a theoretical carcinogenicity concern from telomerase activation; the advisory committee voted 7 to 4 (1 abstention) in favour on 24 July 2026, which is advisory only.","evidence":{"level":"human-small","note":"The evidence is small, mostly from a single research network, and largely not from modern controlled trials. Human: (1) a 2002 report from the originating group that injection beside the eye produced a positive clinical effect in 90% of cases in patients with degenerative retinal lesions (the abstract gives no patient numbers or comparison; a 2025 review's account describes 162 patients and a comparison group on conventional treatment, but no placebo and no between-group results); (2) a small randomised placebo-controlled sublingual study in women aged 40-50 working night shifts (Ivko 2021, 75 women, 40 with low urinary melatonin metabolite split into treatment and placebo groups for 20 days) in which the treated group's metabolite level rose 1.7-fold; sleep outcomes were not assessed and no safety data were reported; FDA noted blinding was not specified and the study was short and small. FDA also listed a related 2021 report on clock-gene expression in night-shift workers. FDA found no study in people with insomnia and no clinical safety study. Animal: monkey hormone studies and mouse lifespan and tumour studies, all with a fixed regimen and (in mice) females only. Cell: telomerase and telomere-length work in human fibroblast cultures. In-vitro rat pineal tissue showed no direct melatonin effect. No phase 2 or 3 trial exists.","sources":[{"url":"https://www.fda.gov/media/193345/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Epitalon-Related Bulk Drug Substances (Epitalon (Free Base) and Epitalon Acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11943447/","title":"Overview of Epitalon: Highly Bioactive Pineal Tetrapeptide with Promising Properties","publisher":"International Journal of Molecular Sciences (via PubMed Central)","date":"2025-03-17","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12195242/","title":"Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa","publisher":"Neuroendocrinology Letters (via PubMed)","date":"2002-08","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/14501183/","title":"Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice","publisher":"Biogerontology (via PubMed)","date":"2003","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12937682/","title":"Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells","publisher":"Bulletin of Experimental Biology and Medicine (via PubMed)","date":"2003-06","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11550036/","title":"Regulatory effect of Epithalon on production of melatonin and cortisol in old monkeys","publisher":"Bulletin of Experimental Biology and Medicine (via PubMed)","date":"2001-04","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12809170/","title":"Effect of a synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) on melatonin secretion by the pineal gland of young and old rats","publisher":"Journal of Endocrinological Investigation (via PubMed)","date":"2003-03","accessed":"2026-09-29"}],"label":"Small human studies"},"route":"No approved route. In the few human studies it was given as a sublingual spray (women working night shifts) and as an injection beside the eye (retinitis pigmentosa, parabulbar). Animal studies used subcutaneous injection in mice and intramuscular injection in monkeys. The products FDA reviewed in 2026 were nominated for subcutaneous injection, but no human study of that route was found. Human absorption and bioavailability are unknown.","halfLife":null,"structure":{"pubchemCid":219042,"pdb":[]},"companies":[],"keyFacts":[{"label":"Approval status","value":"Not approved by FDA or any other regulator we found, and not a component of any FDA-approved drug. There is no USP or NF monograph. FDA's 2026 briefing describes the substances as not well characterised and states no FDA-approved product contains epitalon.","source":{"url":"https://www.fda.gov/media/193345/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Epitalon-Related Bulk Drug Substances (Epitalon (Free Base) and Epitalon Acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"label":"Molecular formula and weight","value":"Free base C14H22N4O9, 390.35 g/mol (sequence Ala-Glu-Asp-Gly); acetate salt 450.40 g/mol. FDA treats the two as different bulk substances.","source":{"url":"https://www.fda.gov/media/193345/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Epitalon-Related Bulk Drug Substances (Epitalon (Free Base) and Epitalon Acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"label":"Orphan designation","value":"Received an FDA orphan drug designation for retinitis pigmentosa on 2 September 2010; it was withdrawn or revoked on 6 January 2016.","source":{"url":"https://www.fda.gov/media/193345/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Epitalon-Related Bulk Drug Substances (Epitalon (Free Base) and Epitalon Acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"label":"FDA advisory committee vote","value":"On 24 July 2026 the Pharmacy Compounding Advisory Committee voted 7 to 4, with 1 abstention, in favour of adding epitalon to the 503A bulks list, against the recommendation of FDA staff. The vote is advisory; notice-and-comment rulemaking would still be needed.","source":{"url":"https://www.mcdermottlaw.com/insights/bulk-list-bound-pcac-backs-majority-of-peptides-in-two-day-public-meeting/","title":"Bulk-List Bound? PCAC Backs Majority of Peptides in Two-Day Public Meeting","publisher":"McDermott Will & Schulte","date":"2026-07-27","accessed":"2026-09-29"}},{"label":"Telomerase in cultured cells","value":"A 2003 report from the originating group found telomerase expression, enzyme activity and telomere elongation in human fetal fibroblast cultures; this is cell-culture evidence only.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/12937682/","title":"Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells","publisher":"Bulletin of Experimental Biology and Medicine (via PubMed)","date":"2003-06","accessed":"2026-09-29"}},{"label":"Mouse lifespan study","value":"In 54 female SHR mice per group, maximum lifespan was 12.3% longer with epitalon, mean lifespan was unchanged and total tumour incidence was unchanged (leukaemia 6.0-fold lower).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/14501183/","title":"Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice","publisher":"Biogerontology (via PubMed)","date":"2003","accessed":"2026-09-29"}}],"safety":[{"text":"No clinical safety studies were found. FDA reported that the nominations included none and that its literature search found none; no pharmacokinetic, acute-toxicity, repeat-dose toxicity or developmental and reproductive toxicity studies were identified either.","source":{"url":"https://www.fda.gov/media/193345/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Epitalon-Related Bulk Drug Substances (Epitalon (Free Base) and Epitalon Acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"Theoretical cancer concern: because epitalon is reported to activate telomerase and lengthen telomeres, and longer telomeres are generally associated with higher cancer risk, FDA said continuous exposure could in principle let cells avoid ageing and become cancerous. The mouse studies were too short and too limited to rule this out.","source":{"url":"https://www.fda.gov/media/193345/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Epitalon-Related Bulk Drug Substances (Epitalon (Free Base) and Epitalon Acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"Injected peptides can trigger immune responses and can clump together (aggregate). FDA said information on aggregation was lacking, so it could not rule out immune reactions, especially with injection. It also listed peptide-related impurities and inconsistent naming (different salts and derivatives sold under the same name) as quality and safety risks.","source":{"url":"https://www.fda.gov/media/193345/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Epitalon-Related Bulk Drug Substances (Epitalon (Free Base) and Epitalon Acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"FDA searched its adverse-event reporting system through 8 December 2025 and found no reports for epitalon. FDA cautioned that this cannot show safety because reporting is voluntary and compounders generally do not report events.","source":{"url":"https://www.fda.gov/media/193345/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, July 23-24, 2026: Evaluation of Epitalon-Related Bulk Drug Substances (Epitalon (Free Base) and Epitalon Acetate) for the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2026-07","accessed":"2026-09-29"}},{"text":"Health Canada listed epitalon among unauthorized injectable peptides it has seized, and warned that unauthorized peptide products carry general risks including infection, allergic reaction, contamination and interactions; it stated that a research-use-only label does not make a product legal. These warnings cover the category, not epitalon specifically.","source":{"url":"https://recalls-rappels.canada.ca/en/alert-recall/think-twice-injecting-peptides-bought-online-unauthorized-products-can-seriously-harm","title":"Think twice before injecting peptides bought online: unauthorized products can seriously harm","publisher":"Health Canada","date":"2026-04-09","accessed":"2026-09-29"}},{"text":"The authors of a 2025 review said that before epitalon could be approved as a drug substance, more studies are needed on short- and long-term toxicity, genotoxicity, carcinogenic potential and interactions.","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11943447/","title":"Overview of Epitalon: Highly Bioactive Pineal Tetrapeptide with Promising Properties","publisher":"International Journal of Molecular Sciences (via PubMed Central)","date":"2025-03-17","accessed":"2026-09-29"}}],"related":["dsip","semax","mots-c","ghk-cu"],"lastVerified":"2026-09-29"},{"slug":"exenatide","name":"Exenatide","url":"https://glp1base.com/molecules/exenatide","aliases":["Exendin-4 (synthetic)","Exendin 4","AC2993","LY2148568","Exenatide once weekly (extended-release form)"],"brands":[{"name":"Byetta","company":"astrazeneca","indication":"Type 2 diabetes in adults (twice-daily form; AstraZeneca told FDA in August 2024 that it planned to permanently stop US marketing)"},{"name":"Bydureon BCise","company":"astrazeneca","indication":"Type 2 diabetes in adults and children aged 10 years and older (once-weekly extended-release form; AstraZeneca told FDA in August 2024 that it planned to permanently stop US marketing)"},{"name":"Bydureon","company":"astrazeneca","indication":"Type 2 diabetes (earlier once-weekly extended-release form; withdrawn from sale in the US in March 2021)"}],"class":"glp1-approved","classLabel":"Approved GLP-1 medicine","targets":["GLP-1 receptor"],"summarySimple":"Exenatide is a lab-made copy of a hormone first found in the saliva of the Gila monster, a large lizard. It acts on the same receptor as the gut hormone GLP-1: it helps the pancreas release insulin when blood sugar is high and slows the stomach. It was approved in the US in 2005 for type 2 diabetes.","summaryExpert":"Exenatide is the synthetic form of exendin-4, a 39-residue peptide amide (C184H282N50O60S, 4186.6 Da) first isolated from Heloderma suspectum venom. Its sequence only partly overlaps human GLP-1; it binds and activates the human GLP-1 receptor, enhancing glucose-dependent insulin secretion, suppressing inappropriately high glucagon and slowing gastric emptying. It carries no fatty-acid chain: it is less prone to enzymatic degradation than native GLP-1 and, according to nonclinical studies, is eliminated mainly by glomerular filtration, giving a terminal half-life of about 2.4 hours (median Tmax 2.1 hours) for the twice-daily immediate-release form, Byetta. Extended-release once-weekly forms (Bydureon, Bydureon BCise) use poly(D,L-lactide-co-glycolide) microspheres to sustain release. FDA first approved Byetta on 28 April 2005 and the EU authorised it on 20 November 2006. In the US, AstraZeneca notified FDA on 16 August 2024 of plans to discontinue Byetta and Bydureon BCise (Bydureon itself left the market in March 2021); FDA approved Amneal's generic exenatide injection (ANDA 206697) on 19 November 2024. Placebo-controlled 16- to 30-week trials showed HbA1c reductions when added to oral agents; EXSCEL (14,752 patients) found the once-weekly form non-inferior to placebo for major cardiovascular events but not superior (HR 0.91, 95% CI 0.83 to 1.00). It has no approved use outside type 2 diabetes; a phase 3 trial in Parkinson's disease reported no benefit and its paper now carries a journal Expression of Concern.","evidence":{"level":"approved","note":"Approved on the basis of phase 3 programmes in type 2 diabetes: placebo-controlled trials of the twice-daily form added to oral drugs (label section 14), DURATION-1 (once-weekly form gave a larger HbA1c fall than twice-daily, -1.9% vs -1.5%), and DURATION-6 (once-weekly exenatide failed non-inferiority against once-daily liraglutide, HbA1c -1.28% vs -1.48%). EXSCEL, a large cardiovascular outcomes trial, found no significant difference in major cardiovascular events (HR 0.91, 95% CI 0.83 to 1.00). Use in Parkinson's disease is unapproved: the UK phase 3 Exenatide-PD3 trial (194 people) found no benefit on motor scores at 96 weeks, and in June 2026 The Lancet published an Expression of Concern about that paper.","sources":[{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021773Orig1s051correctedlbl.pdf","title":"BYETTA (exenatide) injection prescribing information (revised 09/2025)","publisher":"U.S. Food and Drug Administration","date":"2025-09","accessed":"2026-09-29"},{"url":"https://doi.org/10.1016/s0140-6736(08)61206-4","title":"Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study (DURATION-1)","publisher":"The Lancet","date":"2008-09-07","accessed":"2026-09-29"},{"url":"https://doi.org/10.1016/s0140-6736(12)61267-7","title":"Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study","publisher":"The Lancet","date":"2012-11-07","accessed":"2026-09-29"},{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1612917","title":"Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes (EXSCEL)","publisher":"New England Journal of Medicine","date":"2017-09-14","accessed":"2026-09-29"},{"url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02808-3/fulltext","title":"Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3 trial","publisher":"The Lancet","date":"2025-02-04","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42330995/","title":"Expression of Concern: Exenatide once a week versus placebo ... Parkinson's disease in the UK (Lancet 2025;405:627-636)","publisher":"The Lancet (via PubMed)","date":"2026-06-22","accessed":"2026-09-29"}],"label":"Approved"},"route":"Subcutaneous injection. The original form (Byetta) is given twice a day before meals from a prefilled pen; extended-release forms (Bydureon, Bydureon BCise) are given once a week.","halfLife":{"value":"About 2.4 hours (terminal half-life of the twice-daily immediate-release form)","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021773Orig1s051correctedlbl.pdf","title":"BYETTA (exenatide) injection prescribing information (revised 09/2025)","publisher":"U.S. Food and Drug Administration","date":"2025-09","accessed":"2026-09-29"}},"structure":{"pubchemCid":45588096,"pdb":[{"id":"1JRJ","description":"NMR solution structure of exendin-4 (the natural peptide with the same sequence as exenatide) in 30% trifluoroethanol, a helix-promoting solvent; the source paper compares it with GLP-1."},{"id":"3C5T","description":"X-ray structure (2.1 angstrom) of the extracellular domain of the human GLP-1 receptor bound to exendin-4 residues 9-39, showing how the peptide's C-terminal half is held by the receptor."},{"id":"7LLL","description":"Cryo-EM structure (3.7 angstrom) of the full GLP-1 receptor bound to exendin-4 and the Gs protein, showing the active signalling complex."}]},"companies":["astrazeneca"],"keyFacts":[{"label":"First US approval","value":"Byetta was first approved by FDA on 28 April 2005 for type 2 diabetes; the once-weekly Bydureon followed on 27 January 2012 and Bydureon BCise on 20 October 2017.","source":{"url":"https://www.fda.gov/media/189567/download","title":"Pediatric Postmarketing Pharmacovigilance Review: exenatide (Byetta, Bydureon, Bydureon BCise)","publisher":"U.S. Food and Drug Administration","date":"2025-04-14","accessed":"2026-09-29"}},{"label":"Structure","value":"Synthetic 39-amino-acid peptide amide, molecular weight 4186.6 daltons, originally identified in the lizard Heloderma suspectum.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021773Orig1s051correctedlbl.pdf","title":"BYETTA (exenatide) injection prescribing information (revised 09/2025)","publisher":"U.S. Food and Drug Administration","date":"2025-09","accessed":"2026-09-29"}},{"label":"EU authorisation","value":"Byetta was authorised in the European Union on 20 November 2006; the EMA lists AstraZeneca AB as marketing authorisation holder and the medicine as authorised.","source":{"url":"https://www.ema.europa.eu/en/medicines/human/EPAR/byetta","title":"Byetta: EPAR (European public assessment report)","publisher":"European Medicines Agency","date":"2024-11-06","accessed":"2026-09-29"}},{"label":"Monotherapy trial","value":"In a 24-week placebo-controlled trial, HbA1c fell by 0.9% with the higher studied dose versus 0.2% with placebo (difference -0.7%, 95% CI -1.0 to -0.3).","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021773Orig1s051correctedlbl.pdf","title":"BYETTA (exenatide) injection prescribing information (revised 09/2025)","publisher":"U.S. Food and Drug Administration","date":"2025-09","accessed":"2026-09-29"}},{"label":"Cardiovascular outcomes (EXSCEL)","value":"Primary composite events in 11.4% (exenatide) versus 12.2% (placebo); HR 0.91 (95% CI 0.83 to 1.00): non-inferior for safety, not superior for efficacy (P=0.06).","source":{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1612917","title":"Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes (EXSCEL)","publisher":"New England Journal of Medicine","date":"2017-09-14","accessed":"2026-09-29"}},{"label":"US generic","value":"FDA approved a generic exenatide injection from Amneal (ANDA 206697) on 19 November 2024; Drugs@FDA lists it as a prescription product.","source":{"url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=206697","title":"Drugs@FDA: ANDA 206697, Exenatide Synthetic (Amneal)","publisher":"U.S. Food and Drug Administration","date":"2024-11-19","accessed":"2026-09-29"}},{"label":"US marketing status","value":"AstraZeneca notified FDA on 16 August 2024 of plans to permanently discontinue marketing of Byetta and Bydureon BCise; the original Bydureon was withdrawn from sale in March 2021.","source":{"url":"https://www.fda.gov/media/189567/download","title":"Pediatric Postmarketing Pharmacovigilance Review: exenatide (Byetta, Bydureon, Bydureon BCise)","publisher":"U.S. Food and Drug Administration","date":"2025-04-14","accessed":"2026-09-29"}}],"safety":[{"text":"Bydureon BCise carries a boxed warning: exenatide extended-release causes thyroid C-cell tumours at clinically relevant exposures in rats, and it is unknown whether it does so in humans.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2d18cfc4-e0de-4814-a712-c1b7c504bff5","title":"BYDUREON BCISE (exenatide) injectable suspension, extended-release: prescribing information","publisher":"DailyMed, U.S. National Library of Medicine","date":"2025-05","accessed":"2026-09-29"}},{"text":"Most common adverse reactions with Byetta added to metformin and/or a sulfonylurea were gastrointestinal: nausea in 44% versus 18% on placebo, vomiting 13% versus 4%, diarrhoea 13% versus 6%. Nausea usually decreases over time.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021773Orig1s051correctedlbl.pdf","title":"BYETTA (exenatide) injection prescribing information (revised 09/2025)","publisher":"U.S. Food and Drug Administration","date":"2025-09","accessed":"2026-09-29"}},{"text":"With the extended-release form, the most common adverse reactions (5% or more) were injection-site nodules (10.5%) and nausea (8.2%).","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2d18cfc4-e0de-4814-a712-c1b7c504bff5","title":"BYDUREON BCISE (exenatide) injectable suspension, extended-release: prescribing information","publisher":"DailyMed, U.S. National Library of Medicine","date":"2025-05","accessed":"2026-09-29"}},{"text":"Acute pancreatitis, including fatal and non-fatal haemorrhagic or necrotising cases, has been observed with GLP-1 receptor agonists including Byetta; the label says to stop Byetta if pancreatitis is suspected.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021773Orig1s051correctedlbl.pdf","title":"BYETTA (exenatide) injection prescribing information (revised 09/2025)","publisher":"U.S. Food and Drug Administration","date":"2025-09","accessed":"2026-09-29"}},{"text":"Hypoglycaemia risk rises when exenatide is combined with a sulfonylurea or insulin; the label notes the dose of those medicines may need to be reduced.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021773Orig1s051correctedlbl.pdf","title":"BYETTA (exenatide) injection prescribing information (revised 09/2025)","publisher":"U.S. Food and Drug Administration","date":"2025-09","accessed":"2026-09-29"}},{"text":"Postmarketing reports include acute kidney injury (mostly after dehydration from vomiting or diarrhoea), drug-induced immune-mediated thrombocytopenia with serious and possibly fatal bleeding, serious hypersensitivity reactions and pulmonary aspiration during general anaesthesia or deep sedation.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021773Orig1s051correctedlbl.pdf","title":"BYETTA (exenatide) injection prescribing information (revised 09/2025)","publisher":"U.S. Food and Drug Administration","date":"2025-09","accessed":"2026-09-29"}}],"related":["liraglutide","dulaglutide","semaglutide","tirzepatide"],"lastVerified":"2026-09-29"},{"slug":"ghk-cu","name":"GHK-Cu (copper peptide)","url":"https://glp1base.com/molecules/ghk-cu","aliases":["Copper tripeptide-1","Copper tripeptide","GHK copper","Glycyl-L-histidyl-L-lysine copper","Prezatide copper","Cu-GHK"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["No single receptor has been established","Copper(II) transport and binding (competes with albumin for the metal)","Fibroblast extracellular-matrix genes (collagen, glycosaminoglycans, matrix metalloproteinases) in cell and animal studies","TGF-beta pathway gene signatures (cell and gene-expression studies)"],"summarySimple":"GHK-Cu is a tiny protein piece made of three building blocks (glycine, histidine, lysine) holding onto a copper atom. Our blood contains a little of it naturally. It is used in some skin creams. Human studies are few and small, and mostly test creams. Most other claims come from cells or animals. No drug regulator has approved it as a medicine.","summaryExpert":"GHK-Cu is the copper(II) complex of the endogenous tripeptide glycyl-L-histidyl-L-lysine (Gly-His-Lys, GHK; peptide C14H24N6O4, 340.38 Da; the 1:1 copper complex is about 403 Da; INCI copper tripeptide-1, also named prezatide copper). GHK was reported as a growth-promoting tripeptide from human serum in 1973 (Pickart and Thaler). It is a small, unmodified, naturally occurring sequence with no engineering features; copper is coordinated by the N-terminal amine, a deprotonated amide nitrogen and the histidine imidazole, and the solid-state complex is dimeric (Hureau 2011). In equilibrium-dialysis experiments GHK competed with albumin for Cu(II) (about 42% of the copper on the peptide at equimolar concentrations; Lau 1981), consistent with a proposed role in copper transport. No receptor has been established. Proposed actions come from cell culture (stimulation of fibroblast collagen and glycosaminoglycan synthesis, modulation of MMPs and integrins), rodent wound models (effects in dogs, mice and pigs are described in reviews by the discoverer's group), a mouse lung-fibrosis model, a mouse Alzheimer's model, and Connectivity Map gene-expression analyses; the largest claims (for example regulation of thousands of genes, plasma decline with age from about 200 to 80 ng/mL between ages 20 and 60) come mainly from reviews by the discoverer's group and should be read as hypotheses. No human pharmacokinetic or half-life data were verified for this record. Approval status: no major regulator (FDA, EMA, MHRA, PMDA, NMPA, TGA, Health Canada) has approved a GHK-Cu medicine; it is used as a cosmetic ingredient (assessed by the Cosmetic Ingredient Review in 2018 at very low use concentrations). Human evidence is limited to small topical studies: a multicentre randomised trial of a GHK-copper gel in diabetic neuropathic foot ulcers (Mulder 1994, 98.5% vs 60.8% median area closure) and a 13-patient randomised trial after CO2 laser resurfacing that found no significant objective differences (Miller 2006). Injectable and other systemic uses are unapproved and lack controlled human safety data; FDA states (page current as of April 2026) that compounded injectable GHK-Cu may pose immunogenicity risk from aggregation and peptide-related impurities. FDA's May 2026 503A update says GHK-Cu for non-injectable routes will be added back to Category 1 (bulk substances under evaluation); that is not an approval.","evidence":{"level":"human-small","note":"Best available evidence is small, mostly topical, and largely old. Human: a 1994 multicentre randomised, vehicle-controlled trial of a topical GHK-copper gel in diabetic neuropathic plantar ulcers (median area closure 98.5% vs 60.8% for vehicle) and a 2006 randomised trial of 13 patients after CO2 laser resurfacing, which found no statistically significant objective differences in redness resolution, wrinkles or skin quality, only better self-rated skin quality with GHK-Cu (P = .04). Cosmetic-cream studies (12-week facial and eye creams of 41 to 71 women) are reported in review articles by the peptide's discoverer and are not independently verified here. Animal: accelerated wound healing and matrix build-up in rat models (including ischemic wounds), with effects in dogs, mice and pigs described in reviews by the discoverer's group; reduced fibrosis and inflammation in a mouse lung-fibrosis model (GHK peptide); intranasal GHK-Cu in a mouse Alzheimer's model (animal-only). Cell/computational: collagen and glycosaminoglycan synthesis in fibroblasts, Connectivity Map gene signatures. No phase 2 or phase 3 programme for a GHK-Cu drug was found, and no controlled human data for injectable or oral GHK-Cu were verified.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/17147644/","title":"Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper","publisher":"Wound Repair and Regeneration (PubMed)","date":"1994-10","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16847171/","title":"Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin","publisher":"Archives of Facial Plastic Surgery (PubMed)","date":"2006-07","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26236730/","title":"GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration","publisher":"BioMed Research International (PubMed)","date":"2015-07-07","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/14648529/","title":"The effect of topical tripeptide-copper complex on healing of ischemic open wounds","publisher":"Veterinary Surgery (PubMed)","date":"2003-11","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/8227353/","title":"In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds","publisher":"Journal of Clinical Investigation (PubMed)","date":"1993-11","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40766919/","title":"Behavioral and neuropathological features of Alzheimer's disease are attenuated in 5xFAD mice treated with intranasal GHK peptide","publisher":"Aging Pathobiology and Therapeutics (PubMed)","date":"2024-09-30","accessed":"2026-09-29"}],"label":"Small human studies"},"route":"No approved drug route. In human studies GHK-Cu has been tested as a topical gel or cream applied to the skin or to wounds. In animal research it has also been given by injection into wound chambers, into the abdominal cavity and through the nose. Injectable, oral and nasal uses in people are unapproved and have not been studied in controlled human trials that were verified for this record.","halfLife":null,"structure":{"pubchemCid":71587328,"pdb":[]},"companies":[],"keyFacts":[{"label":"Molecular identity","value":"Peptide GHK is C14H24N6O4 (340.38 Da); the 1:1 copper complex (prezatide copper, copper tripeptide-1, CAS 89030-95-5) is about 402.9 Da.","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/71587328","title":"Prezatide copper / GHK-Cu / copper tripeptide-1 (CID 71587328)","publisher":"PubChem, National Library of Medicine","date":"2026","accessed":"2026-09-29"}},{"label":"First described","value":"The peptide was reported as a growth-promoting factor from human serum in 1973 (Pickart and Thaler); it is a natural, unmodified tripeptide.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/4349963/","title":"Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver","publisher":"Nature New Biology (PubMed)","date":"1973-05-16","accessed":"2026-09-29"}},{"label":"Diabetic foot ulcer trial","value":"Multicentre randomised trial of a topical GHK-copper gel: median plantar ulcer area closure 98.5% vs 60.8% for vehicle (P < 0.05); infection incidence 7% vs 34% in ulcers treated immediately after debridement. Published 1994.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/17147644/","title":"Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper","publisher":"Wound Repair and Regeneration (PubMed)","date":"1994-10","accessed":"2026-09-29"}},{"label":"After laser resurfacing trial","value":"13 patients randomised: no significant objective difference in redness resolution, wrinkles or skin quality; self-rated skin quality was better with GHK-Cu (P = .04).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/16847171/","title":"Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin","publisher":"Archives of Facial Plastic Surgery (PubMed)","date":"2006-07","accessed":"2026-09-29"}},{"label":"US compounding status, injectable (April 2026)","value":"FDA lists GHK-Cu for injectable routes among bulk substances previously in Category 2 whose nominations were withdrawn by the nominators, and says there are limited data in humans to inform safety-related considerations.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}},{"label":"US compounding status, non-injectable (May 2026)","value":"FDA's 503A list (updated May 14, 2026) says GHK-Cu for non-injectable routes will be added back to Category 1 (bulk substances under evaluation) after a nominator clarified it had withdrawn only the injectable route. FDA intends to consult its Pharmacy Compounding Advisory Committee before the end of February 2027 on whether to add GHK-Cu to the 503A bulks list.","source":{"url":"https://www.fda.gov/media/94155/download","title":"Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act","publisher":"U.S. Food and Drug Administration","date":"2026-05-14","accessed":"2026-09-29"}}],"safety":[{"text":"Cosmetic use: the Cosmetic Ingredient Review panel concluded copper tripeptide-1 and related peptides are safe in cosmetics at present practices of use and concentration, typically below 10 ppm. This does not cover injectable or higher-strength products.","source":{"url":"https://journals.sagepub.com/doi/10.1177/1091581818807863","title":"Safety Assessment of Tripeptide-1, Hexapeptide-12, Their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in Cosmetics","publisher":"International Journal of Toxicology (Cosmetic Ingredient Review)","date":"2018-11","accessed":"2026-09-29"}},{"text":"FDA states that compounded injectable drugs containing GHK-Cu may pose a risk of immunogenicity because of aggregation and peptide-related impurities, and that there are limited human data to inform safety considerations.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}},{"text":"Australia's regulator (TGA) says unapproved peptide products, including those containing GHK-Cu and often supplied in injectable form, have not been evaluated by the TGA for safety, quality or effectiveness. Adverse events the TGA has received for unapproved peptide products as a group (not attributed to a single peptide) include severe allergic reactions requiring hospitalisation, severe body-wide inflammation, full-body intense itching, palpitations and pain.","source":{"url":"https://www.tga.gov.au/safety/safety-monitoring-and-information/safety-alerts/understanding-your-responsibilities-when-importing-compounding-and-supplying-unapproved-peptide-products","title":"Understanding your responsibilities when importing, compounding and supplying unapproved peptide products","publisher":"Therapeutic Goods Administration (TGA), Australia","date":"2026-04-13","accessed":"2026-09-29"}}],"related":["bpc-157","tb-500","ll-37"],"lastVerified":"2026-09-29"},{"slug":"ipamorelin","name":"Ipamorelin","url":"https://glp1base.com/molecules/ipamorelin","aliases":["NNC 26-0161","Aib-His-D-2Nal-D-Phe-Lys-NH2","ipamorelin acetate","ipamorelin free base"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["Ghrelin receptor (growth hormone secretagogue receptor type 1a, GHSR-1a), agonist"],"summarySimple":"Ipamorelin is a tiny lab-made protein piece (five building blocks) that acts like the hunger hormone ghrelin, even though it is not built like ghrelin. It makes the pituitary gland release a short burst of growth hormone. It is not an approved medicine anywhere we could verify. The one published trial in patients tested gut recovery after bowel surgery and found no clear benefit.","summaryExpert":"Ipamorelin (NNC 26-0161) is a synthetic pentapeptide, H-Aib-His-D-2Nal-D-Phe-Lys-NH2 (C38H49N9O5, 711.9 g/mol), discovered at Novo Nordisk in the 1990s in a series derived from GHRP-1 by removing its central Ala-Trp dipeptide. It is a ghrelin-receptor (GHSR-1a) agonist. Engineering features are a C-terminal amide and three unnatural residues (alpha-aminoisobutyric acid, D-2-naphthylalanine, D-phenylalanine); the peptide is moderately resistant to metabolism, with 60-80% of an intravenous dose recovered intact in bile and urine in rats. In swine, unlike GHRP-2 and GHRP-6, it released GH without raising ACTH or cortisol, even at doses over 200 times the GH ED50. In healthy men, intravenous infusion produced dose-proportional (linear) two-compartment pharmacokinetics with a terminal half-life of about 2 h, clearance 0.078 L/h/kg and steady-state volume 0.22 L/kg, and a single GH pulse peaking near 0.67 h that fell to very low levels by 6 h. The only published efficacy trial is a phase 2 study in postoperative ileus after bowel resection (117 enrolled), which showed no significant difference from placebo; a second, larger phase 2 study (NCT01280344, 320 participants) is registered as completed without posted results. We found no regulator that has approved ipamorelin as a medicine; FDA states it is not a component of any FDA-approved drug and has no USP monograph. In October 2024 FDA's Pharmacy Compounding Advisory Committee voted 0 yes, 12 no, 1 abstain against placing ipamorelin (free base or acetate) on the 503A bulks list, and ipamorelin acetate has been in Category 2 (may present significant safety risks) of FDA's interim 503B bulks policy since 29 September 2023.","evidence":{"level":"phase2","note":"Human evidence is thin and does not support any use. (1) An intravenous pharmacokinetic and pharmacodynamic study in healthy men (1999) showed GH release and a roughly 2-hour half-life. (2) A phase 2 randomised, double-blind, placebo-controlled trial in postoperative ileus after bowel resection (NCT00672074; 117 enrolled, 114 analysed) found no significant difference: median time to first tolerated solid meal was 25.3 h with ipamorelin versus 32.6 h with placebo (p = 0.15). (3) A second phase 2 dose-finding study in the same condition (NCT01280344; 320 participants) is registered as completed, and no results were posted on the registry record. No controlled trial of ipamorelin in growth hormone deficiency, body composition, sleep, ageing or recovery from injury was found on ClinicalTrials.gov, and no phase 3 trial was found. Apart from the gut-recovery trial, the only efficacy data are from rodent studies (for example bone growth and bone mineral content in rats), which are animal-only evidence.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/10496658/","title":"Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers","publisher":"Pharmaceutical Research (via PubMed)","date":"1999-09","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25331030/","title":"Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients","publisher":"International Journal of Colorectal Disease (via PubMed)","date":"2014-12","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT00672074","title":"Safety and Efficacy of Ipamorelin for Management of Post-Operative Ileus (NCT00672074)","publisher":"ClinicalTrials.gov (Helsinn Therapeutics)","date":"2017-04","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT01280344","title":"Safety and Efficacy of Ipamorelin Compared to Placebo for the Recovery of Gastrointestinal Function (NCT01280344)","publisher":"ClinicalTrials.gov (Helsinn Therapeutics)","date":"2017-04","accessed":"2026-09-29"},{"url":"https://www.fda.gov/media/182088/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, October 29, 2024: Evaluation of Ipamorelin-related Bulk Drug Substances for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-10","accessed":"2026-09-29"}],"label":"Phase 2 trials"},"route":"Not approved for any route. In published human studies it was given by intravenous infusion (healthy volunteers, and hospital patients after bowel surgery). In animal studies it has been given by injection into a vein or under the skin, and by nasal application in rats (about 20% nasal bioavailability). Human pharmacokinetic data for other routes were not identified by FDA in its 2024 review.","halfLife":{"value":"About 2 hours (terminal half-life after intravenous infusion in healthy men)","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/10496658/","title":"Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers","publisher":"Pharmaceutical Research (via PubMed)","date":"1999-09","accessed":"2026-09-29"}},"structure":{"pubchemCid":9831659,"pdb":[{"id":"7F9Z","description":"Cryo-EM structure (3.2 A) of the human ghrelin receptor bound to GHRP-6, a related synthetic peptide agonist, in complex with Gq. It does NOT contain ipamorelin; it is the closest experimentally determined view of how a synthetic growth hormone-releasing peptide sits in the ghrelin receptor."},{"id":"7F9Y","description":"Cryo-EM structure of the human ghrelin receptor bound to its natural hormone ghrelin, in complex with Gq. Shows the receptor that ipamorelin activates; it does NOT contain ipamorelin."}]},"companies":["novo-nordisk"],"keyFacts":[{"label":"Chemical identity","value":"Pentapeptide H-Aib-His-D-2Nal-D-Phe-Lys-NH2, formula C38H49N9O5, molecular weight 711.9 g/mol (PubChem CID 9831659).","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/9831659","title":"Ipamorelin (CID 9831659)","publisher":"PubChem, National Library of Medicine","date":"2026","accessed":"2026-09-29"}},{"label":"Approval status","value":"Not a component of any FDA-approved drug, and no USP monograph exists (FDA, 2024).","source":{"url":"https://www.fda.gov/media/182088/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, October 29, 2024: Evaluation of Ipamorelin-related Bulk Drug Substances for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-10","accessed":"2026-09-29"}},{"label":"Half-life in humans","value":"About 2 hours (terminal), clearance 0.078 L/h/kg, steady-state volume 0.22 L/kg after intravenous infusion in healthy men; GH peak near 0.67 hours.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/10496658/","title":"Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers","publisher":"Pharmaceutical Research (via PubMed)","date":"1999-09","accessed":"2026-09-29"}},{"label":"Only published patient efficacy trial","value":"Phase 2 in postoperative ileus after bowel resection: 117 enrolled; median time to first tolerated meal 25.3 h with ipamorelin vs 32.6 h with placebo (p = 0.15), i.e. no significant difference.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/25331030/","title":"Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients","publisher":"International Journal of Colorectal Disease (via PubMed)","date":"2014-12","accessed":"2026-09-29"}},{"label":"FDA advisory committee vote (2024)","value":"On 29 October 2024 the Pharmacy Compounding Advisory Committee voted 0 yes, 12 no, 1 abstain on placing ipamorelin (free base) on the 503A bulks list, and the same for ipamorelin acetate. The vote is advice, not a final FDA decision.","source":{"url":"https://www.fda.gov/media/185412/download","title":"October 29, 2024 Meeting of the Pharmacy Compounding Advisory Committee: Summary Minutes","publisher":"U.S. Food and Drug Administration","date":"2025-01","accessed":"2026-09-29"}},{"label":"FDA 503B interim category","value":"Ipamorelin acetate appears in Category 2 (substances that may present significant safety risks) under FDA's 503B interim policy, added 29 September 2023; FDA page current as of 22 April 2026.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}},{"label":"Status in New Zealand","value":"Medsafe names ipamorelin among unapproved peptide products promoted online; supplying them outside authorised channels is unlawful, and 'for research purposes only' wording does not change that (advisory of 21 May 2026).","source":{"url":"https://www.medsafe.govt.nz/safety/Alerts/Consumer-advisory-Unapproved-peptide-products-health-warning.asp","title":"Consumer advisory: Unapproved peptide products health warning","publisher":"Medsafe (New Zealand Ministry of Health)","date":"2026-05-21","accessed":"2026-09-29"}}],"safety":[{"text":"In the phase 2 postoperative-ileus trial, low potassium (12.5% vs 3.4%), insomnia (10.7% vs 5.2%) and high blood sugar at discharge (14.3% vs 8.6%) were more common with ipamorelin than placebo. Two ipamorelin-treated patients had fatal serious adverse events after surgical complications; whether ipamorelin contributed was unclear. FDA cited these findings as raising safety concerns.","source":{"url":"https://www.fda.gov/media/182088/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, October 29, 2024: Evaluation of Ipamorelin-related Bulk Drug Substances for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-10","accessed":"2026-09-29"}},{"text":"FDA staff were concerned that a GH-releasing peptide could carry the class risks listed for approved growth hormone products (neoplasm, glucose intolerance and diabetes, intracranial hypertension, fluid retention, pancreatitis, among others), and noted QT prolongation with another approved ghrelin-receptor agonist, macimorelin; there are insufficient data to rule these out for ipamorelin.","source":{"url":"https://www.fda.gov/media/182088/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, October 29, 2024: Evaluation of Ipamorelin-related Bulk Drug Substances for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-10","accessed":"2026-09-29"}},{"text":"FDA states that compounded drugs containing ipamorelin acetate may pose a risk of unwanted immune reactions (immunogenicity) for certain routes, because of possible aggregation or peptide-related impurities, and that its unnatural amino acids make the peptide harder to characterise. FDA also says it lacks safety information for certain other injectable routes.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}},{"text":"FDA found no published acute-toxicity or carcinogenicity studies for ipamorelin and only limited nonclinical safety data. Because it acts on ghrelin receptors, FDA noted possible reward-related (reinforcing) effects and possible effects on reproduction and pregnancy, based on ghrelin studies; these were not shown for ipamorelin itself.","source":{"url":"https://www.fda.gov/media/182088/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee, October 29, 2024: Evaluation of Ipamorelin-related Bulk Drug Substances for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-10","accessed":"2026-09-29"}},{"text":"Health Canada warns that unauthorized injectable peptides, including ipamorelin, are illegal and unassessed, and can involve risks such as hormonal imbalance, blood sugar imbalance, infections, wrong or missing active ingredient, and contamination with solvents, particles or bacterial toxins.","source":{"url":"https://recalls-rappels.canada.ca/en/alert-recall/think-twice-injecting-peptides-bought-online-unauthorized-products-can-seriously-harm","title":"Think twice before injecting peptides bought online: unauthorized products can seriously harm you","publisher":"Health Canada","date":"2026-04-09","accessed":"2026-09-29"}}],"related":["cjc-1295","sermorelin","tesamorelin"],"lastVerified":"2026-09-29"},{"slug":"kisspeptin","name":"Kisspeptin","url":"https://glp1base.com/molecules/kisspeptin","aliases":["Kisspeptin-54","KP-54","KP54","Metastin","Metastin (1-54)","KISS1 peptide","Kisspeptin-10","KP-10","Metastin 45-54"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["KISS1R (kisspeptin receptor, also called GPR54): a Gq/11-coupled receptor on GnRH neurons; loss-of-function variants cause hypogonadotropic hypogonadism in people, and cryo-EM structures of the receptor bound to kisspeptin-54 and kisspeptin-10 have been solved","GnRH neurons of the hypothalamus: kisspeptin activates them directly (shown in mice and sheep; supported by human genetics and human hormone responses)","Pituitary gonadotropes (indirectly): LH and FSH release follows the GnRH signal, shown in human studies"],"summarySimple":"Kisspeptin is a natural hormone that acts like a starter switch for the body's reproductive system. It tells a small group of brain cells to send a signal to the pituitary gland. It has been given to volunteers and IVF patients in small, supervised studies. No regulator has approved it as a medicine.","summaryExpert":"Kisspeptin is the family of peptides encoded by KISS1 and processed from a precursor into kisspeptin-54 (metastin, precursor residues 68-121), -14, -13 and -10. They share a C-terminal Arg-Phe-NH2 end, and the shortest active form is kisspeptin-10. Kisspeptin-54 (about 5.8 kDa) was first isolated from human placenta as the endogenous ligand of the orphan receptor now called KISS1R (GPR54) (Ohtaki 2001). The receptor is Gq/11-coupled. Inactivating KISS1R variants cause congenital hypogonadotropic hypogonadism in humans and Gpr54-null mice (Seminara 2003; de Roux 2003), which established kisspeptin as an upstream gatekeeper of pulsatile GnRH secretion. Infundibular (arcuate) kisspeptin neurons that co-express neurokinin B and dynorphin are thought to drive the GnRH pulse generator, and in rodents a rostral (AVPV) kisspeptin population drives the pre-ovulatory LH surge. The molecule discussed here is the unmodified, native peptide, with no engineered half-life extension: kisspeptin-54 has a plasma half-life of about 28 minutes after intravenous infusion in men (Dhillo 2005) and kisspeptin-10 about 4 minutes (Jayasena 2011, as summarised by FDA). The synthetic analogue MVT-602 (previously TAK-448), a modified nonapeptide based on kisspeptin-10, is a separate substance: in two phase 1 studies sustained exposure lowered testosterone to the castration range in men (MacLean 2014), and in phase 1 and 2a trials in women its mean elimination half-life was 1.3-2.2 h (Abbara 2024). In humans, acute intravenous or subcutaneous kisspeptin-54 raises LH, FSH and, in men, testosterone (Dhillo 2005), with the largest LH response in the pre-ovulatory phase in women (Dhillo 2007). Repeated dosing over two weeks in women with hypothalamic amenorrhoea caused tachyphylaxis (Jayasena 2009), matching continuous-infusion desensitisation in monkeys (Seminara 2006). Phase 2 IVF studies at one London centre used a single injection of kisspeptin-54 to trigger oocyte maturation, including in women at high risk of ovarian hyperstimulation syndrome (Jayasena 2014; Abbara 2015, 2017). Intranasal kisspeptin-54 raised LH in a 2025 crossover study. No phase 3 trial exists. No product containing kisspeptin is approved by any regulator. FDA's October 2024 briefing found no approved product containing kisspeptin-10 in any country, and its 503A list, updated 14 May 2026, places kisspeptin-10 in Category 2 (substances raising significant safety concerns).","evidence":{"level":"phase2","note":"Native kisspeptin-54 has been tested in small, supervised human studies: physiology studies in healthy volunteers and patients (usually 5 to 40 people), a few small randomised trials, and single-centre phase 2 IVF trials (53 and 60 women, plus a 62-woman randomised second-dose trial) in which one injection triggered egg maturation. A 2025 crossover study tested a nasal spray. There is no phase 3 trial and no regulatory approval for any indication. Repeated dosing has shown loss of response (tachyphylaxis) in women with hypothalamic amenorrhoea. FDA's 2024 review found the evidence insufficient to judge kisspeptin-10 for male hypogonadism, and no published clinical trial of kisspeptin-10 given for more than one day. Popular claims about weight loss, libido or fertility outside these studies are not established by trials.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/16174713/","title":"Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males","publisher":"Journal of Clinical Endocrinology and Metabolism (Dhillo WS et al.)","date":"2005-12","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25036713/","title":"Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization","publisher":"Journal of Clinical Investigation (Jayasena CN et al.)","date":"2014-08","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26192876/","title":"Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy","publisher":"Journal of Clinical Endocrinology and Metabolism (Abbara A et al.)","date":"2015-09","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28854728/","title":"A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial","publisher":"Human Reproduction (Abbara A et al.)","date":"2017-09-01","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40215751/","title":"Intranasal kisspeptin administration rapidly stimulates gonadotropin release in humans","publisher":"eBioMedicine (Mills EG et al.)","date":"2025-05","accessed":"2026-09-29"},{"url":"https://www.fda.gov/media/182089/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024: Evaluation of Kisspeptin-10 for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-10","accessed":"2026-09-29"}],"label":"Phase 2 trials"},"route":"Not given by any approved route, because no kisspeptin product is approved anywhere. In published clinical research, kisspeptin-54 has been given by intravenous infusion or bolus and by subcutaneous injection under medical supervision, and intranasally in one 2025 crossover study. Kisspeptin-10 has been studied by intravenous and subcutaneous routes. FDA's 2024 review found no human study of intramuscular kisspeptin-10. The synthetic analogue MVT-602 (previously TAK-448) has been studied by subcutaneous injection.","halfLife":{"value":"About 28 minutes for kisspeptin-54 in the blood of healthy men (27.6 +/- 1.1 min, intravenous infusion). Kisspeptin-10 is cleared faster, at about 4 minutes.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/16174713/","title":"Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males","publisher":"Journal of Clinical Endocrinology and Metabolism (Dhillo WS et al.)","date":"2005-12","accessed":"2026-09-29"}},"structure":{"pubchemCid":71306396,"pdb":[{"id":"8XGS","description":"Cryo-EM structure (2.95 A) of the human kisspeptin receptor KISS1R bound to kisspeptin-54 (metastin) and the Gq protein, with an scFv16 stabilising antibody fragment (Science Advances 2024)."},{"id":"8ZJD","description":"Cryo-EM structure (3.06 A) of KISS1R bound to kisspeptin-10, in complex with an engineered Gq protein and scFv16 (Cell Reports 2024). Shows how the shared C-terminal end of all kisspeptins sits in the receptor."}]},"companies":[],"keyFacts":[{"label":"Discovery","value":"Kisspeptin-54 (metastin) was isolated from human placenta in 2001 as a C-terminally amidated, 54-residue peptide that is the natural ligand of the orphan receptor later called KISS1R/GPR54.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/11385580/","title":"Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor","publisher":"Nature (Ohtaki T et al.)","date":"2001-05-31","accessed":"2026-09-29"}},{"label":"Human genetics","value":"Inactivating mutations in the kisspeptin receptor gene GPR54 cause autosomal recessive isolated hypogonadotropic hypogonadism in people (first reported in 2003).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/14573733/","title":"The GPR54 gene as a regulator of puberty","publisher":"New England Journal of Medicine (Seminara SB et al.)","date":"2003-10-23","accessed":"2026-09-29"}},{"label":"First human hormone study","value":"In a double-blind crossover of 6 healthy men, a 90-minute kisspeptin-54 infusion raised mean LH from 4.2 to 10.8 U/L; the plasma half-life was 27.6 +/- 1.1 minutes.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/16174713/","title":"Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males","publisher":"Journal of Clinical Endocrinology and Metabolism (Dhillo WS et al.)","date":"2005-12","accessed":"2026-09-29"}},{"label":"IVF trigger, phase 2","value":"In 60 women at high risk of ovarian hyperstimulation syndrome, one kisspeptin-54 injection led to oocyte maturation in 95%; live birth per embryo transfer was 45% across doses; no woman had moderate, severe or critical OHSS. It was an open-label, single-centre trial without a comparator trigger.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/26192876/","title":"Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy","publisher":"Journal of Clinical Endocrinology and Metabolism (Abbara A et al.)","date":"2015-09","accessed":"2026-09-29"}},{"label":"Approval status","value":"FDA's global database search found no approved product containing kisspeptin-10 in any country, and kisspeptin-10 has no monograph in the European or Japanese pharmacopoeias. FDA proposed against adding it to the 503A bulks list.","source":{"url":"https://www.fda.gov/media/182089/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024: Evaluation of Kisspeptin-10 for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-10","accessed":"2026-09-29"}},{"label":"Molecular size","value":"Kisspeptin-54 is a 54-residue peptide of about 5.8 kDa (PubChem lists 5857 g/mol for C258H401N79O78); kisspeptin-10 is C63H83N17O14, 1302 g/mol.","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/71306396","title":"Kisspeptin (PubChem CID 71306396)","publisher":"PubChem, National Center for Biotechnology Information","date":"2026","accessed":"2026-09-29"}}],"safety":[{"text":"FDA's interim 503A list, updated 14 May 2026, places kisspeptin-10 in Category 2, defined as bulk substances that raise significant safety concerns.","source":{"url":"https://www.fda.gov/media/94155/download","title":"Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (updated May 14, 2026)","publisher":"U.S. Food and Drug Administration","date":"2026-05-14","accessed":"2026-09-29"}},{"text":"Human safety data are limited to short, small studies. FDA's 2024 review found no clinical trial of kisspeptin-10 beyond one day of dosing, and no study of the intramuscular route. It saw no serious adverse events in those short studies, but many did not report adverse events.","source":{"url":"https://www.fda.gov/media/182089/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024: Evaluation of Kisspeptin-10 for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-10","accessed":"2026-09-29"}},{"text":"FDA raised concerns that injected kisspeptin-10 could provoke an immune response (including antibodies that might cross-react with the body's own kisspeptin), and that peptide impurities or clumping could add to this. No study has formally measured immunogenicity.","source":{"url":"https://www.fda.gov/media/182089/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024: Evaluation of Kisspeptin-10 for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-10","accessed":"2026-09-29"}},{"text":"Repeated dosing can stop working: in women with hypothalamic amenorrhoea, the LH response to twice-daily kisspeptin-54 fell sharply over two weeks (tachyphylaxis).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/19820030/","title":"Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis","publisher":"Journal of Clinical Endocrinology and Metabolism (Jayasena CN et al.)","date":"2009-11","accessed":"2026-09-29"}},{"text":"Cell and animal-only signal: in cultured human vascular cells, and in a mouse model prone to atherosclerosis given kisspeptin-10 for four weeks, kisspeptin-10 promoted vascular inflammation and plaque growth. FDA called the human relevance unclear. FDA also noted that its nonclinical toxicity data were too limited to assess safety for clinical use.","source":{"url":"https://www.fda.gov/media/182089/download","title":"FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024: Evaluation of Kisspeptin-10 for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration","date":"2024-10","accessed":"2026-09-29"}},{"text":"In a small 2025 crossover study, intranasal kisspeptin-54 caused no reported side effects or adverse events. One small study is not proof of safety for wider or long-term use.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40215751/","title":"Intranasal kisspeptin administration rapidly stimulates gonadotropin release in humans","publisher":"eBioMedicine (Mills EG et al.)","date":"2025-05","accessed":"2026-09-29"}}],"related":["bremelanotide"],"lastVerified":"2026-09-29"},{"slug":"kpv","name":"KPV","url":"https://glp1base.com/molecules/kpv","aliases":["Lys-Pro-Val","Lysyl-prolyl-valine","alpha-MSH(11-13)","alpha-MSH 11-13","H-Lys-Pro-Val-OH","KPV acetate"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["PepT1 (SLC15A1, di/tripeptide transporter): proposed route into cells, shown in human cell lines and mice","NF-kB and MAP kinase inflammatory signalling: proposed downstream effect, shown in cell studies","Interleukin-1 beta signalling: proposed in a mouse study","Melanocortin receptors: studies indicate they are probably not the main target"],"summarySimple":"KPV is a tiny protein piece made of three building blocks. It is the last three letters of a natural hormone called alpha-MSH. In lab dishes and mice it calmed inflammation. No human studies have been found and no regulator has approved it as a medicine.","summaryExpert":"KPV (Lys-Pro-Val, C16H30N4O4, 342.43 g/mol) is the C-terminal tripeptide of alpha-melanocyte-stimulating hormone (residues 11-13). It is a linear, unmodified, unconjugated tripeptide with no engineered stabilising features; native alpha-MSH is C-terminally amidated, whereas the form FDA and PubChem describe is the free acid, and the acetate salt, N-acetylated KPV, the KdPT analogue and the (CKPV)2 dimer are different substances that the literature sometimes conflates. An early report of anti-inflammatory activity for the alpha-MSH(11-13) fragment came from a mouse ear-swelling model (Hiltz and Lipton, 1989). It does not appear to work through the melanocortin receptors that mediate alpha-MSH's pigmentary and many of its anti-inflammatory effects: it did not raise cAMP in macrophages and it acted in mice with a non-functional MC1R (Getting 2003; Kannengiesser 2008). Proposed mechanisms are uptake by the transporter PepT1 followed by inhibition of NF-kB and MAP-kinase signalling (human Caco2-BBE, HT29-Cl.19A and Jurkat cells) and interference with IL-1 beta effects; the molecular target remains unidentified. In mice, KPV reduced DSS- and TNBS-induced colitis and CD45RBhi transfer colitis, and rodent wound-healing models have been reported. FDA identified no pharmacokinetic study in any species, so there is no half-life. In vitro, KPV did not cross human skin by passive diffusion at detectable levels (Pawar 2017). KPV is not a component of any approved drug, and it has no USAN, USP monograph or UNII. FDA found no study of KPV given to humans, and its search of FAERS and the medical literature for adverse events through 3 December 2025 found no reports. FDA's briefing document (12 May 2026), prepared for the 23-24 July 2026 Pharmacy Compounding Advisory Committee, judged KPV not well characterised and proposed against adding it to the 503A bulks list. The committee voted 8-6 with one abstention to recommend adding it; the vote is advisory only and needs notice-and-comment rulemaking.","evidence":{"level":"animal","note":"The evidence is cell and animal work only. Human intestinal and T-cell lines and mouse colitis models (DSS, TNBS and T-cell transfer colitis) support an anti-inflammatory effect. A mouse peritonitis model and rodent wound models add to this. FDA's 2026 review states that neither the nomination nor its own searches of PubMed, Embase and ClinicalTrials.gov found any study of KPV given to humans by any route. Animal and cell results often do not carry over to people. The oral delivery work in mice is early-stage and used nanoparticle or hydrogel carriers.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/18061177/","title":"PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation","publisher":"Gastroenterology (Dalmasso G et al.)","date":"2008-01","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18092346/","title":"Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease","publisher":"Inflammatory Bowel Diseases (Kannengiesser K et al.)","date":"2008-03","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12750433/","title":"Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides","publisher":"Journal of Pharmacology and Experimental Therapeutics (Getting SJ et al.)","date":"2003-08","accessed":"2026-09-29"},{"url":"https://www.fda.gov/media/193346/download","title":"FDA Briefing Document: Evaluation of KPV-related Bulk Drug Substances (KPV (free base) and KPV acetate) for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration (Pharmacy Compounding Advisory Committee)","date":"2026-05-12","accessed":"2026-09-29"}],"label":"Animal studies only"},"route":"Not given by any approved route, because it is not approved anywhere. In research it has been studied by adding it to drinking water in mice (colitis models), by systemic injection in mouse inflammation models, in nanoparticle or hydrogel carriers designed for oral delivery to the colon in mice, and, in the laboratory only, across excised human skin. No human route has been studied in a published trial.","halfLife":null,"structure":{"pubchemCid":125672,"pdb":[]},"companies":[],"keyFacts":[{"label":"Structure","value":"Lys-Pro-Val tripeptide, C16H30N4O4, molecular weight 342.43 g/mol (free acid); the acetate salt is about 402.5 g/mol.","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/125672","title":"Msh (11-13) / Lys-Pro-Val (L-lysyl-L-prolyl-L-valine), PubChem CID 125672","publisher":"National Center for Biotechnology Information (PubChem)","date":"2005-08-08","accessed":"2026-09-29"}},{"label":"Origin","value":"The C-terminal three residues (11-13) of alpha-melanocyte-stimulating hormone.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/18612139/","title":"Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases","publisher":"Endocrine Reviews (Brzoska T et al.)","date":"2008-08","accessed":"2026-09-29"}},{"label":"US regulatory status","value":"Not a component of any FDA-approved drug and has no USP monograph. In its briefing document dated 12 May 2026 FDA proposed that KPV (free base) and KPV acetate not be added to the 503A bulk drug substances list.","source":{"url":"https://www.fda.gov/media/193346/download","title":"FDA Briefing Document: Evaluation of KPV-related Bulk Drug Substances (KPV (free base) and KPV acetate) for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration (Pharmacy Compounding Advisory Committee)","date":"2026-05-12","accessed":"2026-09-29"}},{"label":"FDA advisory committee vote","value":"On 23 July 2026 the Pharmacy Compounding Advisory Committee voted 8 in favour, 6 against and 1 abstention to recommend adding KPV to the 503A bulks list. The vote is advisory; FDA would still need notice-and-comment rulemaking.","source":{"url":"https://www.mcdermottlaw.com/insights/bulk-list-bound-pcac-backs-majority-of-peptides-in-two-day-public-meeting/","title":"Bulk-list bound? PCAC backs majority of peptides in two-day public meeting","publisher":"McDermott Will & Schulte","date":"2026-07-27","accessed":"2026-09-29"}},{"label":"Human data","value":"FDA found no clinical studies or human exposure data for KPV by any route of administration.","source":{"url":"https://www.fda.gov/media/193346/download","title":"FDA Briefing Document: Evaluation of KPV-related Bulk Drug Substances (KPV (free base) and KPV acetate) for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration (Pharmacy Compounding Advisory Committee)","date":"2026-05-12","accessed":"2026-09-29"}},{"label":"Key preclinical result","value":"Oral KPV reduced the incidence of DSS- and TNBS-induced colitis in mice; the authors attribute the effect to uptake by PepT1, which they showed in human cell lines (mouse and cell-line study).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/18061177/","title":"PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation","publisher":"Gastroenterology (Dalmasso G et al.)","date":"2008-01","accessed":"2026-09-29"}}],"safety":[{"text":"No human safety data exist. FDA states that it did not find clinical studies or human exposure data for KPV, so its safety risks in people are unknown.","source":{"url":"https://www.fda.gov/media/193346/download","title":"FDA Briefing Document: Evaluation of KPV-related Bulk Drug Substances (KPV (free base) and KPV acetate) for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration (Pharmacy Compounding Advisory Committee)","date":"2026-05-12","accessed":"2026-09-29"}},{"text":"FDA searched its adverse event database (FAERS) through 3 December 2025 and found no reports for KPV. FDA notes that this cannot show safety: reporting is voluntary and compounded or unregulated products are rarely reported.","source":{"url":"https://www.fda.gov/media/193346/download","title":"FDA Briefing Document: Evaluation of KPV-related Bulk Drug Substances (KPV (free base) and KPV acetate) for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration (Pharmacy Compounding Advisory Committee)","date":"2026-05-12","accessed":"2026-09-29"}},{"text":"FDA did not identify acute-toxicity, repeat-dose toxicity, genotoxicity, reproductive or carcinogenicity studies of KPV, and no pharmacokinetic studies.","source":{"url":"https://www.fda.gov/media/193346/download","title":"FDA Briefing Document: Evaluation of KPV-related Bulk Drug Substances (KPV (free base) and KPV acetate) for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration (Pharmacy Compounding Advisory Committee)","date":"2026-05-12","accessed":"2026-09-29"}},{"text":"FDA flagged unassessed risks of peptide immunogenicity (anti-drug antibody formation) and aggregation for KPV, and found the substance not well characterised: it is sold under one common name in different salt and derivative forms, and public certificates of analysis lack impurity, aggregate and microbiological testing.","source":{"url":"https://www.fda.gov/media/193346/download","title":"FDA Briefing Document: Evaluation of KPV-related Bulk Drug Substances (KPV (free base) and KPV acetate) for Inclusion on the 503A Bulk Drug Substances List","publisher":"U.S. Food and Drug Administration (Pharmacy Compounding Advisory Committee)","date":"2026-05-12","accessed":"2026-09-29"}},{"text":"Health Canada listed KPV among unauthorized injectable peptides it had seized and warned that such products can carry contamination, infection and allergic-reaction risks, and that 'research use only' labelling does not make them legal.","source":{"url":"https://recalls-rappels.canada.ca/en/alert-recall/think-twice-injecting-peptides-bought-online-unauthorized-products-can-seriously-harm","title":"Think twice before injecting peptides bought online: unauthorized products can seriously harm you","publisher":"Health Canada","date":"2026-04-09","accessed":"2026-09-29"}},{"text":"FDA's list of compounding substances that may present significant safety risks now places KPV under 'nominated but withdrawn' (page content current as of 22 April 2026). The entry says FDA has not identified any human exposure data for KPV by any route and lacks important information on whether it would cause harm in people. Moving off Category 2 is not the same as being added to the 503A bulks list.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}}],"related":["melanotan-ii","bremelanotide","setmelanotide","bpc-157","tb-500","ghk-cu"],"lastVerified":"2026-09-29"},{"slug":"liraglutide","name":"Liraglutide","url":"https://glp1base.com/molecules/liraglutide","aliases":["NN2211","Liraglutide (rDNA origin)"],"brands":[{"name":"Victoza","company":"novo-nordisk","indication":"Type 2 diabetes (adults and children aged 10 years and older); also to reduce the risk of major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease"},{"name":"Saxenda","company":"novo-nordisk","indication":"Chronic weight management with diet and physical activity (adults with obesity, or overweight with at least one weight-related condition; adolescents 12 years and older with obesity and body weight above 60 kg)"}],"class":"glp1-approved","classLabel":"Approved GLP-1 medicine","targets":["GLP-1 receptor"],"summarySimple":"Liraglutide copies a gut hormone called GLP-1. It helps the pancreas release insulin when blood sugar is high, slows the stomach, and turns down hunger signals. A small fatty chain helps it stick to a blood protein, so one daily injection is enough. Its maker says it was the first once-daily GLP-1 medicine for obesity.","summaryExpert":"Liraglutide is an acylated GLP-1 receptor agonist with 97% sequence homology to human GLP-1(7-37): Lys34 is replaced by Arg, and a C16 fatty acid (palmitic acid) is attached to Lys26 through a glutamic acid spacer. Self-association at the injection site, more than 98% plasma protein binding and resistance to DPP-4 and neutral endopeptidase give a plasma half-life of about 13 hours after subcutaneous injection (endogenous GLP-1: 1.5-2 minutes), supporting once-daily use; Tmax is about 11 hours and absolute bioavailability about 55%. Molecular weight is 3751.2 Da (C172H265N43O51). Mechanism: GLP-1R activation raises cAMP via Gs, stimulating insulin and suppressing glucagon secretion in a glucose-dependent manner, delaying gastric emptying and lowering calorie intake without raising 24-hour energy expenditure. Marketed by Novo Nordisk as Victoza (type 2 diabetes; LEADER cardiovascular outcomes trial) and Saxenda (chronic weight management; SCALE programme). It carries a boxed warning for thyroid C-cell tumours seen in rodents. Generic versions have been approved in the US.","evidence":{"level":"approved","note":"Approved by major regulators (FDA, EMA and others) on the basis of large phase 3 programmes: LEAD (type 2 diabetes), LEADER (cardiovascular outcomes, 9,340 participants) and SCALE (weight management), plus a 56-week adolescent trial (251 participants).","sources":[{"url":"https://doi.org/10.1016/S0140-6736(09)60659-0","title":"Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)","publisher":"The Lancet","date":"2009-07-04","accessed":"2026-09-29"},{"url":"https://doi.org/10.1056/NEJMoa1603827","title":"Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes","publisher":"New England Journal of Medicine","date":"2016-07-28","accessed":"2026-09-29"},{"url":"https://doi.org/10.1056/NEJMoa1411892","title":"A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management","publisher":"New England Journal of Medicine","date":"2015-07-02","accessed":"2026-09-29"},{"url":"https://doi.org/10.1056/NEJMoa1916038","title":"A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity","publisher":"New England Journal of Medicine","date":"2020-05-28","accessed":"2026-09-29"}],"label":"Approved"},"route":"Subcutaneous injection, once daily (pre-filled pen, used under a prescriber's supervision)","halfLife":{"value":"About 13 hours after subcutaneous administration","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/206321s020lbl.pdf","title":"SAXENDA (liraglutide) injection prescribing information","publisher":"U.S. Food and Drug Administration","date":"2025-05","accessed":"2026-09-29"}},"structure":{"pubchemCid":16134956,"pdb":[{"id":"4APD","description":"Solution NMR structure (20 conformers) of liraglutide itself: the 31-residue GLP-1(7-37) backbone with the N-hexadecanoyl-L-glutamic acid group (ligand D6M) on Lys26. Deposited in 2012 by Steensgaard, Ludvigsen and colleagues; the linked citation is listed as \"to be published\"."}]},"companies":["novo-nordisk"],"keyFacts":[{"label":"Molecular weight","value":"3751.2 Da (formula C172H265N43O51)","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/206321s020lbl.pdf","title":"SAXENDA (liraglutide) injection prescribing information","publisher":"U.S. Food and Drug Administration","date":"2025-05","accessed":"2026-09-29"}},{"label":"First EU authorisation (Victoza)","value":"30 June 2009, type 2 diabetes; Novo Nordisk A/S is the authorisation holder","source":{"url":"https://www.ema.europa.eu/en/medicines/human/EPAR/victoza","title":"Victoza: EPAR","publisher":"European Medicines Agency","date":"2026-01-16","accessed":"2026-09-29"}},{"label":"First FDA approval (Victoza)","value":"25 January 2010, for blood sugar control in adults with type 2 diabetes","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/022341s000ltr.pdf","title":"NDA 022341 approval letter: Victoza (liraglutide [rDNA origin]) injection","publisher":"U.S. Food and Drug Administration","date":"2010-01-25","accessed":"2026-09-29"}},{"label":"FDA approval for weight management (Saxenda)","value":"23 December 2014; Novo Nordisk described it as the first once-daily GLP-1 analogue for obesity","source":{"url":"https://www.globenewswire.com/news-release/2014/12/23/1600161/0/en/Novo-Nordisk-receives-FDA-approval-for-Saxenda-for-the-treatment-of-obesity.html","title":"Novo Nordisk receives FDA approval for Saxenda for the treatment of obesity","publisher":"Novo Nordisk","date":"2014-12-23","accessed":"2026-09-29"}},{"label":"EU authorisation of Saxenda","value":"Authorised 23 March 2015; the current EU indication covers adults, adolescents (12 years and older) and children (6 to under 12 years) with obesity, and adults with overweight plus a weight-related condition","source":{"url":"https://www.ema.europa.eu/en/medicines/human/EPAR/saxenda","title":"Saxenda: EPAR","publisher":"European Medicines Agency","date":"2025-07-31","accessed":"2026-09-29"}},{"label":"LEADER cardiovascular trial","value":"Major cardiovascular events in 13.0% (608/4,668) vs 14.9% (694/4,672) on placebo; HR 0.87 (95% CI 0.78-0.97)","source":{"url":"https://doi.org/10.1056/NEJMoa1603827","title":"Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes","publisher":"New England Journal of Medicine","date":"2016-07-28","accessed":"2026-09-29"}},{"label":"SCALE weight trial (56 weeks)","value":"Mean weight loss 8.4 kg vs 2.8 kg on placebo; 63.2% vs 27.1% lost at least 5% of body weight","source":{"url":"https://doi.org/10.1056/NEJMoa1411892","title":"A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management","publisher":"New England Journal of Medicine","date":"2015-07-02","accessed":"2026-09-29"}}],"safety":[{"text":"Boxed warning: liraglutide causes thyroid C-cell tumours in rats and mice at clinically relevant exposures; whether it does so in humans, including medullary thyroid carcinoma, is unknown. It is contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5a9ef4ea-c76a-4d34-a604-27c5b505f5a4","title":"VICTOZA (liraglutide) injection label","publisher":"DailyMed (U.S. National Library of Medicine)","date":"2025-10","accessed":"2026-09-29"}},{"text":"In adult weight-management trials the most frequent adverse reactions were nausea (39.3% vs 13.8% placebo), diarrhoea (20.9% vs 9.9%), constipation (19.4% vs 8.5%) and vomiting (15.7% vs 3.9%).","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/206321s020lbl.pdf","title":"SAXENDA (liraglutide) injection prescribing information","publisher":"U.S. Food and Drug Administration","date":"2025-05","accessed":"2026-09-29"}},{"text":"9.8% of adults on the weight-management version stopped because of adverse reactions vs 4.3% on placebo; nausea, vomiting and diarrhoea were the most common reasons.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/206321s020lbl.pdf","title":"SAXENDA (liraglutide) injection prescribing information","publisher":"U.S. Food and Drug Administration","date":"2025-05","accessed":"2026-09-29"}},{"text":"Label warnings include acute pancreatitis, acute gallbladder disease, hypoglycaemia when combined with insulin or insulin secretagogues, increased heart rate, acute kidney injury from volume depletion, severe gastrointestinal reactions, hypersensitivity, suicidal behaviour and ideation (weight-management label), and pulmonary aspiration during general anaesthesia or deep sedation.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/206321s020lbl.pdf","title":"SAXENDA (liraglutide) injection prescribing information","publisher":"U.S. Food and Drug Administration","date":"2025-05","accessed":"2026-09-29"}},{"text":"In the 56-week adolescent trial (251 participants aged 12-17), gastrointestinal adverse events occurred in 64.8% with liraglutide vs 36.5% with placebo, and 10.4% vs 0% stopped treatment because of adverse events.","source":{"url":"https://doi.org/10.1056/NEJMoa1916038","title":"A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity","publisher":"New England Journal of Medicine","date":"2020-05-28","accessed":"2026-09-29"}},{"text":"The Saxenda label states that it may cause fetal harm and that treatment should be discontinued when pregnancy is recognised; it also delays gastric emptying, which may affect absorption of oral medicines.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/206321s020lbl.pdf","title":"SAXENDA (liraglutide) injection prescribing information","publisher":"U.S. Food and Drug Administration","date":"2025-05","accessed":"2026-09-29"}}],"related":["semaglutide","exenatide","dulaglutide","tirzepatide"],"lastVerified":"2026-09-29"},{"slug":"ll-37","name":"LL-37","url":"https://glp1base.com/molecules/ll-37","aliases":["Ropocamptide","Cathelicidin LL-37","Human cathelicidin antimicrobial peptide LL-37","hCAP18(134-170)","CAMP peptide"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["Anionic bacterial membranes and lipopolysaccharide: direct antimicrobial action, shown in laboratory studies","Formyl peptide receptor-like 1 (FPRL1, also called FPR2): white-blood-cell recruitment, shown in human cells in the laboratory","P2X7 receptor: interleukin-1 beta release, shown in human monocytes in the laboratory","Epidermal growth factor receptor (transactivated indirectly): epithelial cell signalling, shown in human airway cells in the laboratory","Self-DNA complexes sensed by Toll-like receptor 9 in plasmacytoid dendritic cells: shown in human psoriasis skin and human cells"],"summarySimple":"LL-37 is a small protein piece that the human body makes itself to fight germs and help skin heal. It has been tested in only a few small human studies, on leg ulcers and on melanoma skin tumours. No regulator has approved it as a medicine, and there is no proof that it works or is safe when used outside a trial.","summaryExpert":"LL-37 (INN ropocamptide; C205H340N60O53, about 4,493 Da) is the 37-residue, C-terminal antimicrobial peptide (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) of hCAP-18, the only human cathelicidin, encoded by CAMP. It corresponds to residues 134-170 of the 170-residue precursor (UniProt P49913). hCAP-18 is stored in neutrophil peroxidase-negative (specific) granules and made by epithelial cells; after release, proteinase 3 cleaves off LL-37 (Sørensen 2001), and the CAMP promoter carries a vitamin D response element, conserved in primates, through which 1,25-dihydroxyvitamin D3 induced CAMP in human myeloid and keratinocyte cell lines (Gombart 2005). The native peptide is unmodified and has no engineered stabilising groups. It is cationic and amphipathic, disordered in water, and forms an alpha-helix with a bend near Gly14-Glu16 in the presence of anions, lipid micelles or membranes; it also oligomerises (Johansson 1998; Wang 2008). Antibacterial activity is membrane-directed; the same peptide was cytotoxic to several eukaryotic cell types at 13-25 micromolar in vitro, and human serum inhibited that activity (Johansson 1998). It is also a signalling molecule: it chemoattracts neutrophils, monocytes and T cells through FPRL1 (Yang 2000), promotes P2X7-dependent IL-1 beta release (Elssner 2004), transactivates EGFR in airway epithelial cells (Tjabringa 2003), and binds self-DNA to trigger TLR9-driven interferon production in plasmacytoid dendritic cells in psoriasis (Lande 2007). I found no published human pharmacokinetic study and no half-life. It is not approved by any regulator I checked. Clinical experience is limited to two small studies: a 34-participant first-in-man randomised, placebo-controlled topical dose-ranging trial in hard-to-heal venous leg ulcers (Grönberg 2014) and a phase 1/2 intratumoral melanoma study (NCT02225366) that enrolled 4 people. FDA lists cathelicidin LL-37 among bulk substances that were nominated for compounding and then withdrawn, and states concerns about immunogenicity for some routes, peptide impurities and characterisation, and nonclinical signals of harm to male reproduction and of tumour promotion in some tissues.","evidence":{"level":"human-small","note":"Human data are limited to two small, early studies. (1) A first-in-man trial in 34 people with hard-to-heal venous leg ulcers: 3-week placebo run-in, then a 4-week randomised, double-blind treatment phase with topical LL-37 or placebo, and 4 weeks of follow-up. The lower two of three strengths healed faster than placebo (healing rate constants about six- and three-fold higher; p = 0.003 and p = 0.088), the highest strength did not differ from placebo, and no safety concerns were reported. (2) A phase 1/2 single-arm study of injections into melanoma skin tumours at MD Anderson (NCT02225366), which enrolled only 4 people; posted results cover 3 and are too small to judge efficacy. A randomised phase 2 diabetic-foot-ulcer cream trial (NCT04098562, planned 40 participants) is registered with unknown status (last known: not yet recruiting, 2019) and no results. Everything else, including the antimicrobial, immune and wound-healing mechanisms, comes from cell, tissue and animal experiments. There is no phase 3 trial and no regulatory approval.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/25041740/","title":"Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial","publisher":"Wound Repair and Regeneration (Grönberg A et al.)","date":"2014-09","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT02225366","title":"Intratumoral Injections of LL37 for Melanoma (NCT02225366)","publisher":"ClinicalTrials.gov (M.D. Anderson Cancer Center)","date":"2021-12-09","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT04098562","title":"Efficacy of LL-37 Cream on Bacteria Colonization, Inflammation Response and Healing Rate of Diabetic Foot Ulcers (NCT04098562)","publisher":"ClinicalTrials.gov (Universitas Indonesia)","date":"2019-09","accessed":"2026-09-29"}],"label":"Small human studies"},"route":"Not given by any approved route, because it is not approved. In clinical studies it has been tested as a topical preparation applied to venous leg ulcers, as injections directly into melanoma skin tumours (intratumoral) at a cancer centre, and, in a registered trial with unknown status, as a cream on diabetic foot ulcers. Systemic use has not been studied in a published human trial that I found.","halfLife":null,"structure":{"pubchemCid":16198951,"pdb":[{"id":"2K6O","description":"Solution NMR structure of full-length human LL-37 in detergent micelles: a curved amphipathic helix-bend-helix (residues 2-31) followed by a disordered C-terminal tail (Wang 2008)."},{"id":"5NMN","description":"Crystal structure of full-length human LL-37 at 0.95 angstrom resolution; the associated paper reports anti-parallel helical dimers and proposes fibril-like assemblies on membranes as the active form."},{"id":"7PDC","description":"Crystal structure of full-length human LL-37 at 1.83 angstroms, crystallised with detergents; the deposited model has two chains, and the associated paper describes a narrow tetrameric channel with a strongly charged core."}]},"companies":[],"keyFacts":[{"label":"Molecule","value":"37 amino acids, C205H340N60O53, molecular weight about 4,493; the INN is ropocamptide. It equals residues 134-170 of the human precursor hCAP-18.","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/16198951","title":"LL-37 (PubChem CID 16198951)","publisher":"National Center for Biotechnology Information (PubChem)","date":"2026","accessed":"2026-09-29"}},{"label":"Where it comes from","value":"LL-37 is cut from the only human cathelicidin precursor, hCAP-18 (170 amino acids; CAMP gene), by proteinase 3 after neutrophil release.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/11389039/","title":"Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3","publisher":"Blood (Sørensen OE et al.)","date":"2001-06","accessed":"2026-09-29"}},{"label":"Only published randomised human trial found","value":"34 participants with hard-to-heal venous leg ulcers; the two lower topical strengths had healing rate constants about six- and three-fold higher than placebo (p = 0.003 and p = 0.088); no safety concerns reported. Published 2014.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/25041740/","title":"Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial","publisher":"Wound Repair and Regeneration (Grönberg A et al.)","date":"2014-09","accessed":"2026-09-29"}},{"label":"Melanoma injection study","value":"NCT02225366 (phase 1/2, MD Anderson, completed 24 November 2020) enrolled 4 participants; results were posted for 3.","source":{"url":"https://clinicaltrials.gov/study/NCT02225366","title":"Intratumoral Injections of LL37 for Melanoma (NCT02225366)","publisher":"ClinicalTrials.gov (M.D. Anderson Cancer Center)","date":"2021-12-09","accessed":"2026-09-29"}},{"label":"Regulatory status in the US","value":"FDA lists cathelicidin LL-37 among bulk drug substances nominated for compounding and then withdrawn by the nominator (page current as of 22 April 2026). No approved drug was identified.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Bulk drug substances used in compounding that may present significant safety risks (Category 2), including the list of nominated but withdrawn substances","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}}],"safety":[{"text":"FDA states compounded drugs containing LL-37 may pose an immunogenicity risk for some routes of administration and complexities with peptide-related impurities and characterisation of the active ingredient, that it lacks enough safety information to know whether the drug would cause harm in humans, and that nonclinical findings suggest detrimental effects on male reproduction and that LL-37 can be protumorigenic in some tissues.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Bulk drug substances used in compounding that may present significant safety risks (Category 2), including the list of nominated but withdrawn substances","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}},{"text":"In laboratory tests, LL-37 was cytotoxic to several kinds of eukaryotic cells at 13-25 micromolar; adding human serum inhibited this cytotoxic effect.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/9452503/","title":"Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37","publisher":"Journal of Biological Chemistry (Johansson J et al.)","date":"1998-02","accessed":"2026-09-29"}},{"text":"In the melanoma injection programme, one patient developed multiple verrucous papules and a blistering lesion with keratoacanthoma-like changes about 45 days after starting injections; the lesions resolved within 2 months of stopping.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/29665030/","title":"Dermatologic toxicity from novel therapy using antimicrobial peptide LL-37 in melanoma: A detailed examination of the clinicopathologic features","publisher":"Journal of Cutaneous Pathology (Dolkar T et al.)","date":"2018-07","accessed":"2026-09-29"}},{"text":"The melanoma study record lists skin squamous cell carcinoma (1 of 2 participants) and actinic keratosis (1 of 2) in the lower-dose cohort, and no serious adverse events or deaths; with only 3 people analysed, causality cannot be judged.","source":{"url":"https://clinicaltrials.gov/study/NCT02225366","title":"Intratumoral Injections of LL37 for Melanoma (NCT02225366)","publisher":"ClinicalTrials.gov (M.D. Anderson Cancer Center)","date":"2021-12-09","accessed":"2026-09-29"}},{"text":"The venous leg ulcer trial (34 participants, 4 weeks of treatment) reported no local or systemic safety concerns with topical use, but it was too small and short to detect uncommon or long-term effects.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/25041740/","title":"Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial","publisher":"Wound Repair and Regeneration (Grönberg A et al.)","date":"2014-09","accessed":"2026-09-29"}},{"text":"A 2023 laboratory and tissue study reported that LL-37 stimulated melanoma cells and macrophages to produce pro-angiogenic and invasion-related factors, and that LL-37 staining increased with melanoma T stage. This is not proof of harm in patients; tumour-promoting potential is unresolved.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/36980564/","title":"LL-37 Might Promote Local Invasion of Melanoma by Activating Melanoma Cells and Tumor-Associated Macrophages","publisher":"Cancers (Ohuchi K et al.)","date":"2023-03","accessed":"2026-09-29"}}],"related":["ghk-cu","kpv","bpc-157"],"lastVerified":"2026-09-29"},{"slug":"maridebart-cafraglutide","name":"Maridebart cafraglutide (MariTide)","url":"https://glp1base.com/molecules/maridebart-cafraglutide","aliases":["MariTide","AMG 133","AMG133","maridebart"],"brands":[],"class":"incretin-pipeline","classLabel":"In clinical trials","targets":["GIP receptor (antagonist antibody)","GLP-1 receptor (agonist peptides)"],"summarySimple":"MariTide is an experimental weight-loss medicine from Amgen. It is built from an antibody that blocks one gut-hormone receptor (GIP) and two small peptides that switch on another (GLP-1). It stays in the body a long time: about three weeks after a dose, roughly half of it is still in the blood. That is why it was tested once a month. It is not approved anywhere yet. Big phase 3 trials are still running.","summaryExpert":"Maridebart cafraglutide (AMG 133, MariTide) is an antibody-peptide conjugate: a fully human IgG1 monoclonal antibody that antagonises the glucose-dependent insulinotropic polypeptide receptor (GIPR), covalently linked at engineered cysteines (E384C) through amino-acid linkers to two GLP-1 receptor agonist peptide analogues (average molecular weight 153,514 Da for the whole conjugate). In cell assays it fully agonised the human GLP-1 receptor (EC50 24.4 pM vs 4.1 pM for native GLP-1) and antagonised human GIPR (IC50 42.4 nM). Attaching the peptides to the antibody gives a mean half-life of about 21 days in humans (phase 1), which the authors link to the every-4-week subcutaneous dosing used in the multiple-dose study. Evidence: first-in-human phase 1 (NCT04478708; 49 participants in single-dose and 26 in multiple-dose cohorts) showed dose-dependent weight loss that persisted for months after the last dose; the 52-week phase 2 trial in obesity (NCT05669599, n=592, NEJM 2025) showed mean weight change of -12.3% to -16.2% (treatment-policy estimand) versus -2.5% with placebo, and HbA1c falls of 1.2 to 1.6 percentage points in the diabetes cohort. Gastrointestinal adverse events were common and, per the trial authors, less frequent with dose escalation and a lower starting dose. It is investigational and not approved by any regulator. As of 2026-09-29, Amgen reports ongoing phase 3 studies (MARITIME-1 and -2 in weight management, plus cardiovascular outcomes, heart failure, sleep apnoea and switch studies); no phase 3 efficacy results were found.","evidence":{"level":"phase2","note":"Best human efficacy data: a randomised, double-blind, placebo-controlled phase 2 trial of 592 adults for 52 weeks, sponsored by Amgen and published in the New England Journal of Medicine (2025), plus a phase 1 first-in-human study (Nature Metabolism 2024). Animal data (obese mice using a mouse-specific surrogate, and obese cynomolgus monkeys) support the design and are animal-only. Phase 3 trials (MARITIME-1, n=3,853; MARITIME-2, n=1,105; primary endpoint body-weight change at week 72) are running with estimated primary completion in early 2027 on ClinicalTrials.gov; no phase 3 results were found as of 2026-09-29. Not approved by any regulator.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/40549887/","title":"Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial","publisher":"New England Journal of Medicine (PubMed)","date":"2025-06-23","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38316982/","title":"A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings","publisher":"Nature Metabolism (PubMed)","date":"2024-02","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT06858839","title":"Evaluation of Maridebart Cafraglutide in Adult Participants Without Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (MARITIME-1, NCT06858839)","publisher":"ClinicalTrials.gov","date":"2025-03-05","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT06858878","title":"Efficacy and Safety of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (MARITIME-2, NCT06858878)","publisher":"ClinicalTrials.gov","date":"2025-03-05","accessed":"2026-09-29"},{"url":"https://www.prnewswire.com/news-releases/amgen-reports-second-quarter-2026-financial-results-302842890.html","title":"Amgen reports second quarter 2026 financial results","publisher":"Amgen (PR Newswire)","date":"2026-08-04","accessed":"2026-09-29"}],"label":"Phase 2 trials"},"route":"Investigational subcutaneous (under-the-skin) injection. In the phase 1 and phase 2 studies it was given every 4 weeks, and in one phase 2 group every 8 weeks. Amgen states that the long-acting design supports starting monthly and later staying on treatment with fewer doses per year; this is being tested in phase 3 and is not an approved regimen.","halfLife":{"value":"About 21 days (mean, first-in-human phase 1 study in people with obesity; about 21 to 24 days for total drug and 14 to 16 days for the intact conjugate across single-dose cohorts)","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10896721/","title":"A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings (full text)","publisher":"Nature Metabolism (PubMed Central)","date":"2024-02","accessed":"2026-09-29"}},"structure":{"pubchemCid":null,"pdb":[]},"companies":["amgen"],"keyFacts":[{"label":"Molecule format","value":"Fully human anti-GIPR IgG1 antibody linked to two GLP-1 analogue peptides; average molecular weight 153,514 Da","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10896721/","title":"A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings (full text)","publisher":"Nature Metabolism (PubMed Central)","date":"2024-02","accessed":"2026-09-29"}},{"label":"Half-life in people","value":"About 21 days (mean, first-in-human phase 1 study)","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10896721/","title":"A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings (full text)","publisher":"Nature Metabolism (PubMed Central)","date":"2024-02","accessed":"2026-09-29"}},{"label":"Phase 2 obesity result (52 weeks)","value":"Mean weight change -12.3% to -16.2% with maridebart cafraglutide versus -2.5% with placebo (treatment-policy estimand; n=465 in the obesity cohort)","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40549887/","title":"Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial","publisher":"New England Journal of Medicine (PubMed)","date":"2025-06-23","accessed":"2026-09-29"}},{"label":"Phase 2 diabetes cohort","value":"Weight change -8.4% to -12.3% versus -1.7% placebo; HbA1c change -1.2 to -1.6 percentage points versus +0.1 with placebo (n=127)","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40549887/","title":"Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial","publisher":"New England Journal of Medicine (PubMed)","date":"2025-06-23","accessed":"2026-09-29"}},{"label":"Regulatory status","value":"Investigational and not approved by any regulator. Phase 3 studies listed by Amgen as ongoing (MARITIME-1 and -2, cardiovascular outcomes, heart failure, sleep apnoea, switch studies)","source":{"url":"https://www.prnewswire.com/news-releases/amgen-reports-second-quarter-2026-financial-results-302842890.html","title":"Amgen reports second quarter 2026 financial results","publisher":"Amgen (PR Newswire)","date":"2026-08-04","accessed":"2026-09-29"}},{"label":"Main phase 3 trial","value":"MARITIME-1 (NCT06858839): 3,853 adults without type 2 diabetes; primary endpoint percent change in body weight at week 72; estimated primary completion January 2027","source":{"url":"https://clinicaltrials.gov/study/NCT06858839","title":"Evaluation of Maridebart Cafraglutide in Adult Participants Without Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (MARITIME-1, NCT06858839)","publisher":"ClinicalTrials.gov","date":"2025-03-05","accessed":"2026-09-29"}}],"safety":[{"text":"In the phase 2 trial, gastrointestinal adverse events were common with maridebart cafraglutide, less frequent with dose escalation and a lower starting dose, and no unexpected safety signals were reported by the authors.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40549887/","title":"Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial","publisher":"New England Journal of Medicine (PubMed)","date":"2025-06-23","accessed":"2026-09-29"}},{"text":"In the phase 1 study the most common adverse events were nausea and vomiting, mostly mild and resolving within 48 hours of administration. In the highest multiple-dose group, only four of eight participants completed all three scheduled doses.","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10896721/","title":"A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings (full text)","publisher":"Nature Metabolism (PubMed Central)","date":"2024-02","accessed":"2026-09-29"}},{"text":"Amgen reports that in the phase 2 trial, discontinuations because of gastrointestinal adverse events in the dose-escalation arms were up to 7.8% and lower than in arms without dose escalation. In a separate phase 1 study of lower starting doses (PK-LDI), overall vomiting incidence was 24.4% and 22.5% with two escalation schedules, with no discontinuations because of gastrointestinal adverse events.","source":{"url":"https://www.amgen.com/newsroom/press-releases/2025/06/results-from-amgens-phase-2-obesity-study-of-monthly-maritide-presented-at-the-american-diabetes-association-85th-scientific-sessions","title":"Results from Amgen's phase 2 obesity study of monthly MariTide presented at the American Diabetes Association 85th Scientific Sessions","publisher":"Amgen","date":"2025-06-23","accessed":"2026-09-29"}},{"text":"Long-term safety is not established. Human data come from phase 1 and phase 2 studies of up to 52 weeks; a cardiovascular outcomes trial (NCT07037433, about 12,800 participants planned) and other phase 3 studies are ongoing. The medicine is unapproved, so it has no regulator-reviewed label or boxed warnings.","source":{"url":"https://clinicaltrials.gov/study/NCT07037433","title":"Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity (MARITIME-CV, NCT07037433)","publisher":"ClinicalTrials.gov","date":"2025-06-25","accessed":"2026-09-29"}}],"related":["tirzepatide","semaglutide","retatrutide"],"lastVerified":"2026-09-29"},{"slug":"mazdutide","name":"Mazdutide","url":"https://glp1base.com/molecules/mazdutide","aliases":["IBI362","LY3305677"],"brands":[{"name":"Xinermei","company":"innovent-biologics","indication":"China only: long-term weight management in adults with obesity or overweight (approved 2025-06-27), and glycaemic control in adults with type 2 diabetes (approved 2025-09)"}],"class":"glp1-approved","classLabel":"Approved GLP-1 medicine","targets":["GLP-1 receptor","Glucagon receptor"],"summarySimple":"Mazdutide is a once-a-week injected medicine that switches on the body's receptors for two hormones: GLP-1, which lowers appetite and helps control blood sugar, and glucagon, which acts mainly on the liver and may help the body use more energy (shown mostly in animals). China approved it in 2025 for weight management and type 2 diabetes. We found no US, EU or UK approval as of September 2026.","summaryExpert":"Mazdutide (IBI362, LY3305677) is a synthetic 33-residue peptide analogue of mammalian oxyntomodulin that acts as a dual agonist of the GLP-1 receptor and the glucagon receptor (GCGR). It carries an Aib substitution at position 2 and a C20 fatty diacid attached through a gamma-Glu and two short PEG-like (OEG) spacers to the epsilon-amine of Lys20 (C207H317N45O65, about 4,476 Da), a fatty-acyl modification intended to extend its time in the body; the C-terminus is amidated. After subcutaneous injection in a phase 1b multiple-ascending-dose study, median Tmax was 72 hours and terminal half-life ranged from 150.9 to 403.5 hours, which supports once-weekly administration. Innovent Biologics develops it in China under an exclusive licence agreement with Eli Lilly (Lilly code LY3305677). China's NMPA approved it on 2025-06-27 for chronic weight management in adults (BMI 28 or more, or 24 or more with at least one weight-related comorbidity) and in September 2025 for glycaemic control in adults with type 2 diabetes. Key trials are GLORY-1 (phase 3, n=610, NEJM), GLORY-2 (higher-dose phase 3, JAMA), DREAMS-1 and DREAMS-2 (phase 3 in type 2 diabetes, Nature) and a US phase 2 trial run by Lilly. No FDA, EMA, MHRA or PMDA approval was found on 2026-09-29. Most efficacy data come from Chinese adults, and long-term cardiovascular outcome data are not yet available.","evidence":{"level":"approved","note":"Approved by China's NMPA (weight management 2025-06-27; type 2 diabetes September 2025). Pivotal evidence is from Chinese adults: GLORY-1 (phase 3, 610 adults with overweight or obesity, 48 weeks), GLORY-2 (phase 3, 461 adults with obesity, 60 weeks) and DREAMS-1 and DREAMS-2 (phase 3, type 2 diabetes). In the US, a completed phase 2 trial in obesity (179 adults, run by Eli Lilly) has been published; no approval by the FDA or other non-Chinese regulators was found in our search.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/40421736/","title":"Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight (GLORY-1)","publisher":"New England Journal of Medicine (PubMed)","date":"2025-06-12","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42251595/","title":"Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial","publisher":"JAMA (PubMed)","date":"2026-08-04","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41407859/","title":"Mazdutide versus placebo in Chinese adults with type 2 diabetes (DREAMS-1)","publisher":"Nature (PubMed)","date":"2026-04","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41407860/","title":"Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes (DREAMS-2)","publisher":"Nature (PubMed)","date":"2026-04","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42628555/","title":"Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2026-08-21","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41028652/","title":"Mazdutide: First Approval","publisher":"Drugs (PubMed)","date":"2025-12","accessed":"2026-09-29"}],"label":"Approved"},"route":"Once-weekly subcutaneous injection, as used in the approved Chinese indications and in all published clinical trials.","halfLife":{"value":"About 6.3 to 16.8 days (150.9 to 403.5 hours) in Chinese adults with overweight or obesity (phase 1b multiple-ascending-dose study, pharmacokinetics measured in 24 participants given mazdutide)","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/34430840/","title":"IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: a randomised, placebo-controlled, multiple ascending dose phase 1b study","publisher":"eClinicalMedicine (PubMed)","date":"2021-08","accessed":"2026-09-29"}},"structure":{"pubchemCid":167312357,"pdb":[]},"companies":["innovent-biologics","eli-lilly"],"keyFacts":[{"label":"First approval","value":"China's NMPA approved mazdutide on 2025-06-27 for chronic weight management in adults with obesity, or overweight with at least one weight-related condition. It was the first dual GCG/GLP-1 receptor agonist approved for this use, according to the developer.","source":{"url":"https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-first-dual-gcgglp-1-receptor-agonist-received-approval-from-chinas-nmpa-for-chronic-weight-management-302493152.html","title":"Innovent Announces Mazdutide, First Dual GCG/GLP-1 Receptor Agonist, Received Approval from China's NMPA for Chronic Weight Management","publisher":"Innovent Biologics (PR Newswire)","date":"2025-06-27","accessed":"2026-09-29"}},{"label":"Type 2 diabetes approval","value":"Approved in China for glycaemic control in adults with type 2 diabetes in September 2025.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/41028652/","title":"Mazdutide: First Approval","publisher":"Drugs (PubMed)","date":"2025-12","accessed":"2026-09-29"}},{"label":"GLORY-1 (phase 3, 610 adults)","value":"Mean weight change at week 48 of -11.00% and -14.01% in the two mazdutide arms versus +0.30% with placebo; 35.7% and 49.5% lost at least 15% of body weight versus 2.0% (treatment-policy estimand).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40421736/","title":"Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight (GLORY-1)","publisher":"New England Journal of Medicine (PubMed)","date":"2025-06-12","accessed":"2026-09-29"}},{"label":"GLORY-2 (phase 3, higher-dose, 461 adults with obesity)","value":"Mean weight change at week 60 of -16.65% versus -1.50% with placebo; 84.3% versus 33.1% lost at least 5%.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42251595/","title":"Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial","publisher":"JAMA (PubMed)","date":"2026-08-04","accessed":"2026-09-29"}},{"label":"US phase 2 (Lilly, 179 adults)","value":"At 32 weeks, least-squares mean weight change ranged from -7.3% to -18.1% across mazdutide regimens versus -0.9% with placebo; 20% stopped treatment for adverse events at the highest regimen.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42628555/","title":"Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2026-08-21","accessed":"2026-09-29"}},{"label":"Half-life","value":"Terminal half-life 150.9 to 403.5 hours (6.3 to 16.8 days) in the phase 1b study; median time to peak level 72 hours.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/34430840/","title":"IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: a randomised, placebo-controlled, multiple ascending dose phase 1b study","publisher":"eClinicalMedicine (PubMed)","date":"2021-08","accessed":"2026-09-29"}}],"safety":[{"text":"The most common adverse events are gastrointestinal and mostly mild to moderate. In GLORY-1, adverse events led to stopping treatment in 1.5%, 0.5% and 1.0% of the lower-dose, higher-dose and placebo groups.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40421736/","title":"Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight (GLORY-1)","publisher":"New England Journal of Medicine (PubMed)","date":"2025-06-12","accessed":"2026-09-29"}},{"text":"In the higher-dose GLORY-2 trial, vomiting occurred in 53.1% versus 1.3% with placebo, nausea in 46.9% versus 3.2% and diarrhoea in 39.4% versus 6.5%; 2.9% versus 0% stopped for adverse events.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42251595/","title":"Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial","publisher":"JAMA (PubMed)","date":"2026-08-04","accessed":"2026-09-29"}},{"text":"In the US phase 2 trial, stopping treatment because of adverse events was most frequent at the highest regimen (20%), mainly from gastrointestinal disorders.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42628555/","title":"Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2026-08-21","accessed":"2026-09-29"}},{"text":"High-dose glucagon can acutely raise heart rate; in clinical studies, mazdutide's heart-rate increase has generally been similar to that of GLP-1 receptor agonists, and blood pressure fell.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42535526/","title":"Cardiovascular Effects of Glucagon Receptor Signaling Alone and Combined With Glucagon-Like Peptide-1 Receptor Signaling in Multiagonists: A Narrative Review With a Translational Focus","publisher":"Journal of the American Heart Association (PubMed)","date":"2026-08-04","accessed":"2026-09-29"}},{"text":"Evidence is mainly from Chinese adults; reviewers note that longer-term, multi-ethnic and cardiovascular safety data are still needed.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42410325/","title":"Efficacy and Safety of the Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist Mazdutide in Predominantly Chinese Adults With Obesity and/or Type 2 Diabetes: A Systematic Review and Meta-Analysis","publisher":"Diabetes, Obesity and Metabolism (PubMed)","date":"2026-07-06","accessed":"2026-09-29"}}],"related":["retatrutide","survodutide","tirzepatide","semaglutide","cagrilintide"],"lastVerified":"2026-09-29"},{"slug":"melanotan-ii","name":"Melanotan II","url":"https://glp1base.com/molecules/melanotan-ii","aliases":["MT-II","MT2","MTII","Melanotan 2","Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["Melanocortin receptors (non-selective agonist; MC1R, MC3R and MC4R are the best-documented targets)"],"summarySimple":"Melanotan II is a small lab-made peptide that copies a natural hormone which darkens skin and acts in the brain. It was tested in a few small human studies between 1996 and 2000, and we found no regulator that has approved it. In Australia and the UK it is sold illegally as a tanning product, and regulators warn about its side effects.","summaryExpert":"Melanotan II (MT-II) is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone (alpha-MSH): Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, closed by a lactam bridge between the Asp and Lys side chains (C50H69N15O9, about 1,024 Da). It came from a 1989 design programme that cyclised the alpha-MSH 4-10 core by lactam bridging with Nle4 and D-Phe7 substitutions; the 23-membered-ring analogues were about 90-100-fold more potent than alpha-MSH in a lizard-skin bioassay and showed prolonged residual activity. It is a non-selective melanocortin receptor agonist: MC1R activation on melanocytes explains skin darkening, while activation of central MC3R/MC4R is thought to underlie appetite suppression in mice and, in men, penile erection and increased sexual desire. We found no published human pharmacokinetic study, so no half-life is stated. Human evidence is limited to a 3-volunteer pilot phase 1 study (1996), two small double-blind placebo-controlled crossover studies in men with erectile dysfunction (1998 and 2000; 10 men each), and a 2000 review by the same group summarising its experience in 20 men with psychogenic or organic erectile dysfunction; nausea, yawning and stretching were common. We found no later phase 2 or 3 trial and no marketing approval from any regulator. The TGA states it is a prescription-only medicine in Australia with no product on the Australian register, and the MHRA treats Melanotan II as a medicine (unauthorised) when it is sold as an injectable or pen. Case reports link unregulated products to eruptive or atypical naevi, melanoma, priapism, rhabdomyolysis, renal infarction and posterior reversible encephalopathy syndrome; causality for melanoma is unproven. In the US it was removed from FDA's 503A Category 2 list in April 2026 after its nomination was withdrawn (FDA now lists it under 'nominated but withdrawn'), and the Pharmacy Compounding Advisory Committee is due to consider it before the end of February 2027; removal from Category 2 does not make it an approved drug and does not automatically give it Category 1 status. Bremelanotide (Vyleesi) is a closely related analogue that differs at the C-terminus (free acid rather than amide).","evidence":{"level":"human-small","note":"The best available human data are a 3-volunteer pilot phase 1 study (skin darkening, spontaneous erections, nausea) and two small double-blind, placebo-controlled crossover studies in men with erectile dysfunction (10 men with psychogenic ED and 10 men with organic risk factors), plus a 2000 review by the same group summarising its results in 20 men; all were published between 1996 and 2000. They showed erections and higher sexual desire but were tiny, short, and proof-of-concept only. We found no large randomised trial for tanning, sexual dysfunction or any other use, and we found no regulator that has approved it. The appetite-suppression findings come from mouse experiments in which the peptide was injected directly into the brain; this is animal-only evidence and has not been shown to work as a treatment in people.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/8637402/","title":"Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study","publisher":"Life Sciences (PubMed)","date":"1996","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9679884/","title":"Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study","publisher":"The Journal of Urology (PubMed)","date":"1998-08","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11018622/","title":"Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction","publisher":"Urology (PubMed)","date":"2000-10","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11035391/","title":"Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II","publisher":"International Journal of Impotence Research (PubMed)","date":"2000-10","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/8990120/","title":"Role of melanocortinergic neurons in feeding and the agouti obesity syndrome","publisher":"Nature (PubMed)","date":"1997-01-09","accessed":"2026-09-29"}],"label":"Small human studies"},"route":"In the human studies it was given by subcutaneous injection under medical supervision; in the mouse feeding experiments it was injected directly into the brain (intracerebroventricular). It has no approved route because it has no approved use. Regulators describe the unapproved products sold for tanning as injectables and nasal sprays whose contents are not verified.","halfLife":null,"structure":{"pubchemCid":92432,"pdb":[]},"companies":[],"keyFacts":[{"label":"Molecular identity","value":"Cyclic heptapeptide, formula C50H69N15O9, molecular weight about 1,024 Da (PubChem CID 92432)","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/92432","title":"melanotan-II (PubChem CID 92432)","publisher":"National Center for Biotechnology Information, PubChem","date":"2026-09-29","accessed":"2026-09-29"}},{"label":"First human study (1996)","value":"Pilot phase 1 study in 3 healthy men: 2 of 3 showed increased skin pigmentation; intermittent spontaneous erections over 1-5 hours after dosing and mild nausea were also reported","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/8637402/","title":"Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study","publisher":"Life Sciences (PubMed)","date":"1996","accessed":"2026-09-29"}},{"label":"Psychogenic erectile dysfunction study (1998)","value":"Erections in 8 of 10 men; mean tip rigidity above 80% lasted 38.0 minutes with MT-II versus 3.0 minutes with placebo (p=0.0045)","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/9679884/","title":"Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study","publisher":"The Journal of Urology (PubMed)","date":"1998-08","accessed":"2026-09-29"}},{"label":"Review of 20 men (2000)","value":"A review by the same research group reported erection without sexual stimulation in 17 of 20 men with psychogenic or organic erectile dysfunction; increased desire after 13/19 (68%) MT-II doses versus 4/21 (19%) placebo doses (P<0.01)","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/11035391/","title":"Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II","publisher":"International Journal of Impotence Research (PubMed)","date":"2000-10","accessed":"2026-09-29"}},{"label":"Australian status","value":"Prescription-only medicine in Australia, not approved as a tanning agent, and no product containing it is on the Australian Register of Therapeutic Goods (TGA, 17 August 2026)","source":{"url":"https://www.tga.gov.au/safety/safety-monitoring-and-information/safety-alerts/melanotan-ii-tanning-peptide-products-found-be-inconsistently-dosed","title":"Melanotan II tanning peptide products found to be inconsistently dosed","publisher":"Therapeutic Goods Administration (TGA), Australia","date":"2026-08-17","accessed":"2026-09-29"}},{"label":"US compounding status","value":"On 15 April 2026 it was one of 12 peptides removed from FDA's 503A Category 2 list after the nominations were withdrawn; the Pharmacy Compounding Advisory Committee is due to consider it before the end of February 2027. Removal from Category 2 does not automatically give Category 1 status, and it is not an approved drug.","source":{"url":"https://www.mcdermottlaw.com/insights/bulk-list-bound-pcac-backs-majority-of-peptides-in-two-day-public-meeting/","title":"Bulk-list bound? PCAC backs majority of peptides in two-day public meeting","publisher":"McDermott Will & Schulte","date":"2026-07-27","accessed":"2026-09-29"}}],"safety":[{"text":"In the first human study, mild nausea occurred at most dose levels, one volunteer had grade II somnolence and fatigue at the highest dose, and intermittent spontaneous erections over 1-5 hours after dosing came with a stretching-and-yawning pattern.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/8637402/","title":"Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study","publisher":"Life Sciences (PubMed)","date":"1996","accessed":"2026-09-29"}},{"text":"A case report describes a painful erection lasting about 22 hours (low-flow priapism) after melanotan injection that needed hospital treatment to drain blood from the penis; at 4-week follow-up erections were short-lived and could not be sustained.","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6388891/","title":"Melanotan-induced priapism: a hard-earned tan","publisher":"BMJ Case Reports (PubMed Central)","date":"2019-02-21","accessed":"2026-09-29"}},{"text":"FDA states compounded drugs containing Melanotan II may pose a risk of immunogenicity for certain routes of administration because of possible aggregation or peptide-related impurities, and that published case reports describe melanoma, posterior reversible encephalopathy syndrome, sympathomimetic toxidrome and priapism.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}},{"text":"A case report of injected Melanotan II, confirmed by mass spectrometry, described sympathomimetic excess (fast heart rate, sweating, anxiety, tremor) and rhabdomyolysis with kidney injury needing intensive care.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/23121206/","title":"Melanotan II injection resulting in systemic toxicity and rhabdomyolysis","publisher":"Clinical Toxicology (PubMed)","date":"2012-12","accessed":"2026-09-29"}},{"text":"Unapproved products are not checked for quality: the MHRA states the contents of unauthorised medicines are unknown and there are no safeguards that they meet standards for quality, safety or effectiveness.","source":{"url":"https://assets.publishing.service.gov.uk/media/669fbd3aa3c2a28abb50d55a/Final_Redaction_FOI_24_274.pdf","title":"FOI 24/274 - Side effects reports of melanotan II products","publisher":"Medicines and Healthcare products Regulatory Agency (MHRA), UK","date":"2024-04-17","accessed":"2026-09-29"}},{"text":"TGA laboratory testing of five seized bottles of one Melanotan II nasal-spray product found the estimated amount varied more than twofold between bottles; the TGA warns this inconsistency increases the chance of adverse events.","source":{"url":"https://www.tga.gov.au/safety/safety-monitoring-and-information/safety-alerts/melanotan-ii-tanning-peptide-products-found-be-inconsistently-dosed","title":"Melanotan II tanning peptide products found to be inconsistently dosed","publisher":"Therapeutic Goods Administration (TGA), Australia","date":"2026-08-17","accessed":"2026-09-29"}},{"text":"Melanotan-induced skin darkening does not protect against UV exposure the way a suitable sunscreen does, according to the TGA.","source":{"url":"https://www.tga.gov.au/news/blog/dont-risk-using-tanning-products-containing-melanotan","title":"Don't risk using tanning products containing melanotan","publisher":"Therapeutic Goods Administration (TGA), Australia","date":"2025-01-24","accessed":"2026-09-29"}}],"related":["bremelanotide","setmelanotide"],"lastVerified":"2026-09-29"},{"slug":"mots-c","name":"MOTS-c","url":"https://glp1base.com/molecules/mots-c","aliases":["Mitochondrial open reading frame of the 12S rRNA-c","Mitochondrial-derived peptide MOTS-c","MOTSC"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["No confirmed receptor. Reported to act inside cells: folate cycle and purine synthesis inhibition leading to AMPK activation, and nuclear gene regulation (including NRF2-linked antioxidant response genes) after entering the nucleus"],"summarySimple":"MOTS-c is a tiny protein piece that your own cells make from their mitochondria, the parts that produce energy. In mice and cell studies it changes how muscle handles sugar and fat. It is not an approved medicine anywhere we could verify, and there are no published results from trials of MOTS-c itself in people.","summaryExpert":"MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a 16-residue peptide, MRWQEMGYIFYPRKLR (C101H152N28O22S2, 2174.6 Da), encoded by a short open reading frame inside the mitochondrial MT-RNR1 (12S rRNA) gene; it was described in 2015 (Lee et al., Cell Metab). It is a natural, unmodified linear peptide; FDA notes it can be made by standard solid-phase peptide synthesis. Proposed mechanism: in cells it inhibits the folate cycle and de novo purine biosynthesis, raising AICAR and activating AMPK; under metabolic stress it translocates to the nucleus in an AMPK-dependent way and interacts with stress-responsive transcription factors such as NRF2 (Kim et al., 2018). No cell-surface receptor has been established, and FDA reviewers noted that the molecular target remains unknown. In mice, injected MOTS-c reduced diet-induced obesity and insulin resistance and improved physical performance in young, middle-aged and old animals; rodent and cell work also reports effects on bone cells, vascular calcification and pancreatic islet senescence. No in-vivo pharmacokinetic study was identified by FDA; the only pharmacokinetic-type data found was in-vitro degradation in human whole blood, which is rapid. In humans, endogenous MOTS-c rose in skeletal muscle (11.9-fold after exercise) and plasma (1.6-fold during exercise) in 10 healthy young men, and circulating levels are reported lower in type 2 diabetes, but these are observations rather than treatment trials. MOTS-c has no approval from any regulator we verified. The only completed clinical trial linked to the peptide used CB4211, a modified analogue (CohBar phase 1a/1b, NCT03998514, 88 enrolled), which the sponsor reported as well tolerated, with a liver-fat reduction similar to placebo in its small phase 1b portion. A phase 2a trial of MOTS-c in prediabetes with overweight or obesity (NCT07505745) is registered as recruiting, with no results. In the US, MOTS-c is a non-approved substance; the FDA's Pharmacy Compounding Advisory Committee voted 7-5 (2 abstentions) on 23 July 2026 to recommend it for the 503A Bulks List (as reported by AJMC), against FDA staff's written proposal not to add it. That vote is non-binding and no final FDA decision had been verified.","evidence":{"level":"animal","note":"For MOTS-c itself the published therapeutic evidence is animal (mainly mice and rats) and cell work, plus human observational data (levels rise with exercise and are reported lower in type 2 diabetes). FDA's 2026 briefing document states it identified no clinical studies or human exposure data for MOTS-c by any route. The only completed human trial connected to the peptide tested CB4211, a modified analogue, in a phase 1a/1b safety study (NCT03998514); the sponsor reported acceptable tolerability, and although liver enzymes (ALT, AST) and glucose fell more than on placebo in the 20-person phase 1b portion, the reported drop in liver fat (MRI-PDFF) was about the same as placebo (5.03% vs 4.88%). A phase 2a trial of MOTS-c in prediabetes (NCT07505745, sponsor Hudson Biotech, estimated 120 participants) began in February 2026 and has no results yet. Animal effects should not be assumed to carry over to people.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/25738459/","title":"The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance","publisher":"Cell Metabolism (via PubMed)","date":"2015-03-03","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33473109/","title":"MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis","publisher":"Nature Communications (via PubMed)","date":"2021-01-20","accessed":"2026-09-29"},{"url":"https://www.fda.gov/media/193347/download","title":"FDA Briefing Document for MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate), Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"US Food and Drug Administration","date":"2026-05-11","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT03998514","title":"A Phase 1a/1b Study of CB4211 in Healthy Non-obese Subjects and Subjects With Nonalcoholic Fatty Liver Disease (NCT03998514)","publisher":"ClinicalTrials.gov (CohBar, Inc.)","date":"2021-05-11","accessed":"2026-09-29"},{"url":"https://www.globenewswire.com/news-release/2021/08/10/2278324/0/en/CohBar-Announces-Positive-Topline-Results-from-the-Phase-1a-1b-Study-of-CB4211-Under-Development-for-NASH-and-Obesity.html","title":"CohBar Announces Positive Topline Results from the Phase 1a/1b Study of CB4211 Under Development for NASH and Obesity","publisher":"CohBar, Inc. (GlobeNewswire)","date":"2021-08-10","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT07505745","title":"MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity (NCT07505745)","publisher":"ClinicalTrials.gov (Hudson Biotech)","date":"2026-04-01","accessed":"2026-09-29"}],"label":"Animal studies only"},"route":"No approved route because there is no approved product. In published animal studies MOTS-c has been given by injection (for example into the abdominal cavity of mice). The completed human trial of the analogue CB4211 and the registered phase 2a trial of MOTS-c both list subcutaneous injection. FDA's 2026 review found no clinical studies or human exposure data for MOTS-c by any route, including by mouth.","halfLife":null,"structure":{"pubchemCid":146675088,"pdb":[]},"companies":[],"keyFacts":[{"label":"What it is","value":"A 16-amino-acid peptide (MRWQEMGYIFYPRKLR), formula C101H152N28O22S2, molecular weight 2174.6 g/mol, encoded within the mitochondrial 12S rRNA gene and first described in 2015.","source":{"url":"https://www.fda.gov/media/193347/download","title":"FDA Briefing Document for MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate), Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"US Food and Drug Administration","date":"2026-05-11","accessed":"2026-09-29"}},{"label":"Regulatory status (US)","value":"As of FDA's 11 May 2026 briefing, MOTS-c and its acetate were not components of any FDA-approved drug and had no USP/NF monograph; FDA identified no clinical studies or human exposure data for MOTS-c.","source":{"url":"https://www.fda.gov/media/193347/download","title":"FDA Briefing Document for MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate), Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"US Food and Drug Administration","date":"2026-05-11","accessed":"2026-09-29"}},{"label":"FDA advisory committee vote","value":"On 23 July 2026 the Pharmacy Compounding Advisory Committee voted 7-5 with 2 abstentions to recommend MOTS-c for the 503A Bulks List, against FDA staff's written recommendation. The vote is non-binding; FDA makes the final decision.","source":{"url":"https://www.ajmc.com/view/fda-panel-backs-6-peptides-for-compounding","title":"FDA Panel Backs 6 Peptides for Compounding","publisher":"The American Journal of Managed Care","date":"2026-07-31","accessed":"2026-09-29"}},{"label":"Completed human trial (analogue only)","value":"CB4211, a modified MOTS-c analogue, was tested in a placebo-controlled phase 1a/1b study (NCT03998514): phase 1a in 65 healthy adults, phase 1b in 20 obese adults with NAFLD. In the 4-week phase 1b portion (11 on CB4211, 9 on placebo) ALT changed by -21% vs +4% and AST by -28% vs -11%, but the reported liver-fat reduction was 5.03% vs 4.88%, essentially the same.","source":{"url":"https://www.globenewswire.com/news-release/2021/08/10/2278324/0/en/CohBar-Announces-Positive-Topline-Results-from-the-Phase-1a-1b-Study-of-CB4211-Under-Development-for-NASH-and-Obesity.html","title":"CohBar Announces Positive Topline Results from the Phase 1a/1b Study of CB4211 Under Development for NASH and Obesity","publisher":"CohBar, Inc. (GlobeNewswire)","date":"2021-08-10","accessed":"2026-09-29"}},{"label":"Human exercise data","value":"In 10 sedentary healthy young men, endogenous MOTS-c rose 11.9-fold in skeletal muscle after cycling and 1.6-fold in plasma during cycling; plasma levels returned to baseline after 4 hours of rest.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/33473109/","title":"MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis","publisher":"Nature Communications (via PubMed)","date":"2021-01-20","accessed":"2026-09-29"}},{"label":"Ongoing MOTS-c trial","value":"A phase 2a, randomised, placebo-controlled trial in adults with prediabetes and overweight/obesity (NCT07505745, sponsor Hudson Biotech, estimated 120 participants) was recruiting as of March 2026; primary completion is estimated for February 2027 and no results are posted.","source":{"url":"https://clinicaltrials.gov/study/NCT07505745","title":"MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity (NCT07505745)","publisher":"ClinicalTrials.gov (Hudson Biotech)","date":"2026-04-01","accessed":"2026-09-29"}}],"safety":[{"text":"FDA's 2026 review found no clinical studies or human exposure data for MOTS-c by any route, so its safety risks in humans are unknown; it also found no in-vivo pharmacokinetic, acute toxicity, genotoxicity, reproductive or carcinogenicity studies.","source":{"url":"https://www.fda.gov/media/193347/download","title":"FDA Briefing Document for MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate), Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"US Food and Drug Administration","date":"2026-05-11","accessed":"2026-09-29"}},{"text":"FDA searches of its adverse event database (through 9 March 2025) retrieved no reports for MOTS-c, but FDA notes compounders generally do not report adverse events, so absence of reports is not evidence of safety.","source":{"url":"https://www.fda.gov/media/193347/download","title":"FDA Briefing Document for MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate), Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"US Food and Drug Administration","date":"2026-05-11","accessed":"2026-09-29"}},{"text":"FDA is concerned that an injected 16-amino-acid peptide could provoke an immune response, and that impurities or peptide aggregation in formulated products could raise this risk; FDA found only limited information on MOTS-c immunogenicity and could not rule this risk out.","source":{"url":"https://www.fda.gov/media/193347/download","title":"FDA Briefing Document for MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate), Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"US Food and Drug Administration","date":"2026-05-11","accessed":"2026-09-29"}},{"text":"Product identity is a documented problem: MOTS-c is a common name rather than a formal nonproprietary name, and FDA has seen different salts and derivatives, including different active moieties, sold under the same name; FDA calls this a safety risk because patients may receive a different substance than the one ordered.","source":{"url":"https://www.fda.gov/media/193347/download","title":"FDA Briefing Document for MOTS-c-Related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate), Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"US Food and Drug Administration","date":"2026-05-11","accessed":"2026-09-29"}},{"text":"For the analogue CB4211 (not MOTS-c itself), the sponsor reported no serious adverse events in its phase 1a/1b study; the only adverse events in more than 10% of treated participants were mild to moderate injection-site reactions.","source":{"url":"https://www.globenewswire.com/news-release/2021/08/10/2278324/0/en/CohBar-Announces-Positive-Topline-Results-from-the-Phase-1a-1b-Study-of-CB4211-Under-Development-for-NASH-and-Obesity.html","title":"CohBar Announces Positive Topline Results from the Phase 1a/1b Study of CB4211 Under Development for NASH and Obesity","publisher":"CohBar, Inc. (GlobeNewswire)","date":"2021-08-10","accessed":"2026-09-29"}}],"related":["elamipretide","nad-plus","aod-9604"],"lastVerified":"2026-09-29"},{"slug":"nad-plus","name":"NAD+","url":"https://glp1base.com/molecules/nad-plus","aliases":["Nicotinamide adenine dinucleotide","Nadide","NAD","Coenzyme I","Diphosphopyridine nucleotide (DPN, older name)"],"brands":[],"class":"other","classLabel":"Other","targets":["Not a receptor-targeted drug. NAD+ is a coenzyme used by hundreds of enzymes: dehydrogenases (as an electron carrier, cycling with NADH) and NAD+-consuming enzymes such as sirtuins, poly(ADP-ribose) polymerases (PARPs) and the NADases CD38 and CD157"],"summarySimple":"NAD+ is a helper molecule that every cell in your body already makes and uses, to turn food into energy and to run repair jobs. Some clinics sell NAD+ drips as wellness treatments. Studies in people are few and small, and we found no US FDA approval. Whether drips help healthy people has not been shown.","summaryExpert":"NAD+ (nicotinamide adenine dinucleotide; INN nadide) is an endogenous dinucleotide coenzyme: two nucleotides (adenosine monophosphate and nicotinamide mononucleotide) joined through their phosphate groups. It is not a peptide. PubChem lists the oxidised form as C21H28N7O14P2+ (664.4 g/mol; the neutral inner-salt record is 663.4 g/mol). Biology: NAD+/NADH shuttle electrons in glycolysis, the TCA cycle and oxidative phosphorylation, and NAD+ is also consumed as a substrate by sirtuins, PARPs and CD38/CD157. Cells make it from tryptophan (de novo), from nicotinic acid (Preiss-Handler pathway), from nicotinamide (salvage) and from the precursors nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Pharmacology of the exogenous molecule: it is a large, highly polar, charged molecule. In the only human intravenous pharmacokinetic pilot identified (Grant et al., 2019; 8 infused, 3 saline controls), infused NAD+ was completely removed from plasma for at least the first 2 hours, which the authors attribute to tissue uptake and/or metabolism; plasma NAD+ and metabolites then rose by the end of the 6-hour infusion, and the metabolite pattern was consistent with NAD+ glycohydrolase and pyrophosphatase activity. Breakdown to smaller molecules (nicotinamide, ADP-ribose, NMN and others) therefore appears to be a major fate, but how much intact NAD+ reaches cells in humans is unresolved. Some intact uptake has been shown in cultured cells (Billington et al., 2008). No human half-life was identified. Evidence: oral NR and NMN reliably raise blood NAD+ metabolites in humans and are generally well tolerated, but functional outcomes are heterogeneous or null; a 2026 PRISMA systematic review found no eligible outcome trials of intravenous or intramuscular NAD+ itself for anti-ageing or wellness use. The main randomised, placebo-controlled trial of intravenous NAD+ identified is a single-centre Chinese trial in 180 patients with ischaemic heart failure (LVEF at 1 month 45.44% vs 42.44%, p=0.024; clinical event differences not significant; ChiCTR2200059169). A 2026 multi-cohort study found human whole-blood NAD+ does not fall with age, which weakens the rationale for using blood NAD+ as an ageing biomarker. Status: the trial paper reports that the NAD+ it used carried a Chinese drug approval number (SFDA H41024721); we could not independently confirm its approved indications on the NMPA database. We found no US FDA (Drugs@FDA) approval, and no approval by EMA, MHRA, TGA, Health Canada or PMDA was verified. In the US, NAD and NADH are listed in FDA's 503A Category 1 (bulk substances under evaluation, with interim enforcement discretion for compounding) as of the 14 May 2026 update; this is not an approval and not a final bulks-list decision. Health Canada named NAD+ among unauthorized injectable products in an April 2026 advisory.","evidence":{"level":"human-small","note":"For NAD+ itself the human evidence is small. The main randomised, placebo-controlled trial identified is in 180 adults with heart failure from ischaemic cardiomyopathy, intravenous NAD+ for 7 days on top of standard care; single centre in China; primary endpoint LVEF at 1 month improved, 45.44 +/- 8.55% vs 42.44 +/- 9.09%, p=0.024; NT-proBNP, 6-month cardiac events and NYHA class showed non-significant trends; the authors note the trial was underpowered for clinical events; the trial paper also cites a smaller Chinese pilot randomised trial in older heart-failure patients). There is also one small randomised, saline-controlled pilot of the blood and urine fate of an infusion in healthy volunteers (Grant et al., 2019; 8 infused, 3 controls), plus uncontrolled series and case reports summarised in 2026 reviews. A 2026 systematic review found no eligible outcome trials of intravenous or intramuscular NAD+ for anti-ageing or wellness; a 2026 critical review calls IV longevity therapy experimental. Most of the wider 'NAD+ boosting' evidence concerns oral precursors (NR, NMN), which raise blood NAD+ metabolites in humans with mixed functional results, and is not evidence about NAD+ drips. Mechanistic claims about ageing come largely from mice and cell studies.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/40954388/","title":"Effect of Nicotinamide Adenine Dinucleotide on Heart Failure Caused by Ischemic Cardiomyopathy: A Randomized, Placebo-Controlled Trial (Yu et al.)","publisher":"American Journal of Cardiovascular Drugs (via PubMed)","date":"2026-01","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31572171/","title":"A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+ (Grant et al.)","publisher":"Frontiers in Aging Neuroscience (via PubMed)","date":"2019","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41655607/","title":"NAD+ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence (Gallagher et al.)","publisher":"Ageing Research Reviews (via PubMed)","date":"2026-04","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42787547/","title":"Narrative review of intravenous NAD+ and NAD+ precursors in wellness and translational medicine (Alangari et al.)","publisher":"Frontiers in Aging (via PubMed)","date":"2026","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41915584/","title":"Intravenous longevity therapy: a critical review of evidence, mechanisms, and clinical utility (Godic et al.)","publisher":"Acta Dermatovenerologica Alpina, Pannonica et Adriatica (via PubMed)","date":"2026-03","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27721479/","title":"Nicotinamide riboside is uniquely and orally bioavailable in mice and humans (Trammell et al.)","publisher":"Nature Communications (via PubMed)","date":"2016-10-10","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29599478/","title":"Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults (Martens et al.)","publisher":"Nature Communications (via PubMed)","date":"2018-03-29","accessed":"2026-09-29"}],"label":"Small human studies"},"route":"In the human studies identified, NAD+ itself was given by intravenous infusion: a 7-day course in the Chinese heart-failure trial and a single 6-hour infusion in the healthy-volunteer pharmacokinetic pilot. Wellness-clinic intravenous and injectable NAD+ is not an approved use we could verify anywhere. Oral NAD+ has not been established as a way to raise NAD+; the oral studies in humans used the precursors nicotinamide riboside or nicotinamide mononucleotide instead.","halfLife":null,"structure":{"pubchemCid":5893,"pdb":[{"id":"2I65","description":"Human CD38 (ADP-ribosyl cyclase 1, a mutant form used to trap the substrate) with NAD in the catalytic pocket. Shows how one of the body's main NAD+-consuming enzymes holds the molecule (primary citation: J Biol Chem 2006)."},{"id":"1U8F","description":"Human placental glyceraldehyde-3-phosphate dehydrogenase (GAPDH) at 1.75 angstrom resolution with NAD bound as its cofactor. Shows NAD+ in its classic role as an electron carrier in glycolysis."}]},"companies":[],"keyFacts":[{"label":"US FDA compounding status","value":"NAD and NADH are listed in FDA's 503A Category 1 (bulk drug substances under evaluation, with interim enforcement discretion for compounding) in the update of 14 May 2026. This is not FDA approval and not a final decision on the 503A bulks list. A different salt form (beta-NAD disodium salt trihydrate) is listed in Category 3, 'nominated without adequate support'.","source":{"url":"https://www.fda.gov/media/94155/download","title":"Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (categories list, updated May 14, 2026)","publisher":"US Food and Drug Administration","date":"2026-05-14","accessed":"2026-09-29"}},{"label":"FDA Category 1 meaning","value":"FDA says it does not intend to take action against compounding with Category 1 substances if specified conditions are met, until it decides on inclusion in the 503A bulks list. Substances nominated on or after 7 January 2025 are not placed in these categories.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act","title":"Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act","publisher":"US Food and Drug Administration","date":"2026-05-14","accessed":"2026-09-29"}},{"label":"Health Canada advisory","value":"On 2026-04-09 Health Canada listed NAD+ among examples of unauthorized injectable peptide drugs it had seized, and stated that unauthorized drug products are illegal in Canada and not assessed for safety, efficacy and quality.","source":{"url":"https://recalls-rappels.canada.ca/en/alert-recall/think-twice-injecting-peptides-bought-online-unauthorized-products-can-seriously-harm","title":"Think twice before injecting peptides bought online: unauthorized products can seriously harm you","publisher":"Health Canada","date":"2026-04-09","accessed":"2026-09-29"}},{"label":"Randomised trial in heart failure","value":"180 adults with ischaemic cardiomyopathy: LVEF at 1 month 45.44 +/- 8.55% with intravenous NAD+ vs 42.44 +/- 9.09% with placebo (p = 0.024); 6-month cardiac events 14.6% vs 24.7% (p = 0.089, not significant). The paper states the NAD+ used carried a Chinese drug approval number (SFDA Approved No. H41024721).","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12779688/","title":"Effect of Nicotinamide Adenine Dinucleotide on Heart Failure Caused by Ischemic Cardiomyopathy: full text (Yu et al.)","publisher":"American Journal of Cardiovascular Drugs (via PubMed Central)","date":"2026-01","accessed":"2026-09-29"}},{"label":"Human infusion pharmacokinetics","value":"In a pilot of a 6-hour intravenous NAD+ infusion in healthy volunteers, plasma NAD+ and its metabolites did not change until after 2 hours, consistent with rapid removal of infused NAD+ from plasma, and rose about 4-fold by the end of the infusion; urine contained NAD+ itself and methylnicotinamide.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/31572171/","title":"A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+ (Grant et al.)","publisher":"Frontiers in Aging Neuroscience (via PubMed)","date":"2019","accessed":"2026-09-29"}},{"label":"Blood NAD+ and age","value":"Across seven independent human cohorts, whole-blood NAD+ stayed stable with age and lifestyle interventions but changed, as expected, with nicotinamide riboside supplementation, challenging blood NAD+ as an ageing biomarker.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42135539/","title":"Human whole-blood NAD+ levels do not vary with age or lifestyle interventions (Trętowicz et al.)","publisher":"Nature Metabolism (via PubMed)","date":"2026-06","accessed":"2026-09-29"}}],"safety":[{"text":"Infusion-related effects reported in human intravenous NAD+ studies include nausea, abdominal discomfort, cramping, flushing and chest pressure or discomfort. Long-term safety data are lacking, and the review describes the evidence as insufficient to support routine clinical or wellness use.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42787547/","title":"Narrative review of intravenous NAD+ and NAD+ precursors in wellness and translational medicine (Alangari et al.)","publisher":"Frontiers in Aging (via PubMed)","date":"2026","accessed":"2026-09-29"}},{"text":"In the 180-patient heart-failure trial, adverse events were rare: one patient in the NAD+ group had brief dizziness (treatment stopped as a precaution) and one placebo patient had chest discomfort; no significant laboratory abnormalities were reported. The trial was short and small, so it cannot rule out less common harms.","source":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12779688/","title":"Effect of Nicotinamide Adenine Dinucleotide on Heart Failure Caused by Ischemic Cardiomyopathy: full text (Yu et al.)","publisher":"American Journal of Cardiovascular Drugs (via PubMed Central)","date":"2026-01","accessed":"2026-09-29"}},{"text":"A 2026 critical review of intravenous 'longevity' therapy (infusions of vitamins, glutathione, NAD+ and similar agents) says it should be regarded as experimental, citing scarce and underpowered placebo-controlled trials, pharmacokinetic limitations, procedural risks and very variable infusion protocols.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/41915584/","title":"Intravenous longevity therapy: a critical review of evidence, mechanisms, and clinical utility (Godic et al.)","publisher":"Acta Dermatovenerologica Alpina, Pannonica et Adriatica (via PubMed)","date":"2026-03","accessed":"2026-09-29"}},{"text":"Health Canada warns that unauthorized injectable products, a list that includes NAD+, may contain too much, too little or none of the stated ingredient, may contain contaminants such as solvents, heavy metals and particles, and may cause infections, allergic reactions and other serious complications.","source":{"url":"https://recalls-rappels.canada.ca/en/alert-recall/think-twice-injecting-peptides-bought-online-unauthorized-products-can-seriously-harm","title":"Think twice before injecting peptides bought online: unauthorized products can seriously harm you","publisher":"Health Canada","date":"2026-04-09","accessed":"2026-09-29"}}],"related":["mots-c","elamipretide","epitalon"],"lastVerified":"2026-09-29"},{"slug":"orforglipron","name":"Orforglipron","url":"https://glp1base.com/molecules/orforglipron","aliases":["LY3502970","OWL833"],"brands":[{"name":"Foundayo","company":"eli-lilly","indication":"Weight management in adults with obesity, or overweight with a weight-related condition (oral tablet, US and UK); also authorised in the UK for type 2 diabetes"}],"class":"glp1-oral","classLabel":"Oral GLP-1","targets":["GLP-1 receptor"],"summarySimple":"Orforglipron is a once-a-day tablet that copies a gut hormone called GLP-1. Most drugs like it are peptides that must be injected. This one is a small, non-peptide molecule that survives being swallowed. It is approved in the US and UK for weight management. The UK has also approved it for type 2 diabetes.","summaryExpert":"Orforglipron (LY3502970, OWL833) is an orally available, non-peptide, small-molecule agonist of the human GLP-1 receptor (free base C48H48F2N10O5, about 883 Da; the marketed drug substance is the calcium salt). It binds a pocket in the upper helical bundle formed by the extracellular domain, extracellular loop 2 and transmembrane helices 1, 2, 3 and 7. It is a partial agonist biased toward G-protein activation over beta-arrestin recruitment. Its interaction with the primate-specific Trp33 of the receptor's extracellular domain explains its species selectivity, and the label states it is not pharmacologically active in rats or mice. After oral dosing, maximum concentration is reached in 4 to 8 hours, absolute bioavailability is about 77 to 79%, plasma protein binding exceeds 99%, and elimination half-life is about 29 to 49 hours, supporting once-daily use with or without food. It is cleared mainly by hepatic CYP3A4 oxidation and faecal excretion. The FDA approved it as Foundayo on 2026-04-01 for chronic weight management, based on the phase 3 ATTAIN-1 (NCT05869903) and ATTAIN-2 (NCT05872620) trials; the MHRA authorised it on 2026-08-10 for weight management and type 2 diabetes. ACHIEVE-1 (NCT05971940) is a key phase 3 diabetes trial. It carries the class boxed warning for thyroid C-cell tumours.","evidence":{"level":"approved","note":"Approved by the US FDA (2026-04-01, weight management) and the UK MHRA (2026-08-10, weight management and type 2 diabetes). The US approval rests on two 72-week randomised, double-blind, placebo-controlled phase 3 trials (ATTAIN-1 in adults without diabetes, n=3,127; ATTAIN-2 in adults with type 2 diabetes, n=1,613). Phase 3 work continues in other conditions. A July 2026 review in Drugs reported submissions for regulatory review in the EU, Japan and Canada; no decision there was found.","sources":[{"url":"https://www.nejm.org/doi/abs/10.1056/NEJMoa2511774","title":"Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (ATTAIN-1)","publisher":"New England Journal of Medicine","date":"2025-09-16","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40544435/","title":"Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes (ACHIEVE-1)","publisher":"New England Journal of Medicine (PubMed)","date":"2025-09-18","accessed":"2026-09-29"},{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220934Orig1s000lbl.pdf","title":"FOUNDAYO (orforglipron) tablets, for oral use: prescribing information","publisher":"U.S. Food and Drug Administration","date":"2026-04","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42479349/","title":"Orforglipron: First Approval","publisher":"Drugs (PubMed)","date":"2026-07-21","accessed":"2026-09-29"}],"label":"Approved"},"route":"Oral tablet taken once daily, with or without food, swallowed whole (from the approved US label).","halfLife":{"value":"About 29 to 49 hours after an oral dose","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220934Orig1s000lbl.pdf","title":"FOUNDAYO (orforglipron) tablets, for oral use: prescribing information","publisher":"U.S. Food and Drug Administration","date":"2026-04","accessed":"2026-09-29"}},"structure":{"pubchemCid":137319706,"pdb":[{"id":"6XOX","description":"Cryo-EM structure (3.1 A) of the human GLP-1 receptor bound to orforglipron (LY3502970) and a Gs protein complex, showing the small molecule in a pocket of the upper helical bundle. Released 2020-11-18."}]},"companies":["eli-lilly"],"keyFacts":[{"label":"FDA approval","value":"Approved by the US FDA on 2026-04-01 as Foundayo for weight management in adults with obesity, or overweight with at least one weight-related condition. It was the first new molecular entity approved under the FDA's National Priority Voucher programme.","source":{"url":"https://www.fda.gov/news-events/press-announcements/fda-approves-first-new-molecular-entity-under-national-priority-voucher-program","title":"FDA Approves First New Molecular Entity Under National Priority Voucher Program","publisher":"U.S. Food and Drug Administration","date":"2026-04-01","accessed":"2026-09-29"}},{"label":"UK approval","value":"Authorised by the MHRA on 2026-08-10 for weight management and for improving blood-sugar control in type 2 diabetes; prescription-only, and described as not currently available on the NHS.","source":{"url":"https://www.gov.uk/government/news/uk-first-in-europe-to-authorise-orforglipron-for-weight-management-and-type-2-diabetes","title":"UK first in Europe to authorise orforglipron for weight management and type 2 diabetes","publisher":"Medicines and Healthcare products Regulatory Agency (GOV.UK)","date":"2026-08-10","accessed":"2026-09-29"}},{"label":"ATTAIN-1 result","value":"In 3,127 adults with obesity and no diabetes, mean weight change at week 72 was -7.5% to -11.2% across three doses versus -2.1% with placebo (P<0.001).","source":{"url":"https://www.nejm.org/doi/abs/10.1056/NEJMoa2511774","title":"Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (ATTAIN-1)","publisher":"New England Journal of Medicine","date":"2025-09-16","accessed":"2026-09-29"}},{"label":"ACHIEVE-1 result","value":"In 559 adults with early type 2 diabetes, HbA1c fell by 1.24 to 1.48 percentage points at week 40 versus 0.41 with placebo; body weight change was -4.5% to -7.6% versus -1.7%.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/40544435/","title":"Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes (ACHIEVE-1)","publisher":"New England Journal of Medicine (PubMed)","date":"2025-09-18","accessed":"2026-09-29"}},{"label":"Half-life","value":"About 29 to 49 hours after an oral dose","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220934Orig1s000lbl.pdf","title":"FOUNDAYO (orforglipron) tablets, for oral use: prescribing information","publisher":"U.S. Food and Drug Administration","date":"2026-04","accessed":"2026-09-29"}},{"label":"Molecular weight","value":"About 883 for the free base (C48H48F2N10O5); the calcium salt used in the tablets is 902.0. It is not a peptide.","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/137319706","title":"Orforglipron (CID 137319706)","publisher":"PubChem, National Center for Biotechnology Information","date":"2019-01-28","accessed":"2026-09-29"}}],"safety":[{"text":"Boxed warning: risk of thyroid C-cell tumours. Rodent thyroid tumours are seen with GLP-1 receptor agonists that are active in rats and mice. Orforglipron is not active in rodents and produced no rodent tumours, and the relevance to humans is not determined. It is contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220934Orig1s000lbl.pdf","title":"FOUNDAYO (orforglipron) tablets, for oral use: prescribing information","publisher":"U.S. Food and Drug Administration","date":"2026-04","accessed":"2026-09-29"}},{"text":"Gastrointestinal effects were the most common adverse reactions in the two pooled weight-management trials. Nausea occurred in 26% to 35% across dose groups versus 10% with placebo, vomiting in 13% to 24% versus 4%, and constipation in 20% to 27% versus 9%.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220934Orig1s000lbl.pdf","title":"FOUNDAYO (orforglipron) tablets, for oral use: prescribing information","publisher":"U.S. Food and Drug Administration","date":"2026-04","accessed":"2026-09-29"}},{"text":"Stopping treatment because of gastrointestinal adverse reactions happened in 3% to 6% of people on orforglipron versus 0.7% on placebo. Severe gastrointestinal reactions were reported in about 3% versus 1%.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220934Orig1s000lbl.pdf","title":"FOUNDAYO (orforglipron) tablets, for oral use: prescribing information","publisher":"U.S. Food and Drug Administration","date":"2026-04","accessed":"2026-09-29"}},{"text":"The label lists warnings for acute pancreatitis (6 adjudicated cases in orforglipron-treated patients versus 1 placebo patient in the pooled trials), acute kidney injury from dehydration, gallbladder disease, hypersensitivity reactions and hypoglycaemia (more likely with a sulfonylurea or insulin).","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220934Orig1s000lbl.pdf","title":"FOUNDAYO (orforglipron) tablets, for oral use: prescribing information","publisher":"U.S. Food and Drug Administration","date":"2026-04","accessed":"2026-09-29"}},{"text":"Because it delays gastric emptying, there are rare reports with GLP-1 receptor agonists of pulmonary aspiration during general anaesthesia or deep sedation.","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220934Orig1s000lbl.pdf","title":"FOUNDAYO (orforglipron) tablets, for oral use: prescribing information","publisher":"U.S. Food and Drug Administration","date":"2026-04","accessed":"2026-09-29"}},{"text":"In ATTAIN-1, adverse events led to treatment discontinuation in 5.3% to 10.3% of people on orforglipron and 2.7% on placebo.","source":{"url":"https://www.nejm.org/doi/abs/10.1056/NEJMoa2511774","title":"Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (ATTAIN-1)","publisher":"New England Journal of Medicine","date":"2025-09-16","accessed":"2026-09-29"}}],"related":["semaglutide","tirzepatide","retatrutide"],"lastVerified":"2026-09-29"},{"slug":"pramlintide","name":"Pramlintide","url":"https://glp1base.com/molecules/pramlintide","aliases":["Pramlintide acetate","Amylin analogue (human amylin analog)","AC137"],"brands":[{"name":"Symlin (SymlinPen)","company":"astrazeneca","indication":"Adjunct to mealtime insulin in type 1 and type 2 diabetes (US)"}],"class":"amylin","classLabel":"Amylin analogue","targets":["Amylin receptors (calcitonin receptor paired with RAMP1, RAMP2 or RAMP3)"],"summarySimple":"Pramlintide is a lab-made, slightly changed version of amylin, a hormone your pancreas releases along with insulin when you eat. It slows how fast food leaves the stomach, lowers a hormone that raises blood sugar, and helps you feel full. In the US it was approved as an add-on to mealtime insulin. The FDA now lists all Symlin products as discontinued.","summaryExpert":"Pramlintide is a 37-residue synthetic analogue of human amylin (IAPP). It differs from the human peptide by proline substitutions at positions 25, 28 and 29, which limit the self-aggregation seen with native amylin; it keeps the Cys2-Cys7 disulfide and C-terminal amide (molecular weight about 3949 Da). It acts as an agonist at amylin receptors, heterodimers of the calcitonin receptor and a RAMP. In humans it slows gastric emptying, blunts the meal-related rise in glucagon and reduces energy intake. After subcutaneous injection, absolute bioavailability is about 30-40% and the half-life in healthy people is about 48 minutes; the main metabolite, des-Lys1 pramlintide, is active in vitro. The FDA approved it in March 2005 (Symlin, NDA 021332) as an adjunct for people with type 1 or type 2 diabetes who use mealtime insulin and have not reached glycaemic goals. The label carries a boxed warning for severe hypoglycaemia. In 52-week randomised trials it lowered HbA1c from baseline by roughly 0.3-0.6 percentage points at week 52, significantly more than placebo, with modest weight loss instead of weight gain, and nausea was the commonest adverse effect. Phase 2 studies in obesity (published 2007-2008) showed weight loss, but pramlintide is not approved for weight management and that use is unapproved. Drugs@FDA lists all Symlin products as discontinued. Approval status at other regulators was not verified for this record.","evidence":{"level":"approved","note":"Approved by the US FDA in 2005 on the strength of randomised, double-blind, placebo-controlled 26- to 52-week trials in type 1 and type 2 diabetes (mealtime add-on to insulin). Weight-management studies were phase 2 only (a 16-week study and a 4-month study with an 8-month extension) and did not lead to an obesity approval; that use is unapproved.","sources":[{"url":"https://doi.org/10.2337/diacare.25.4.724","title":"A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes","publisher":"Diabetes Care","date":"2002-04","accessed":"2026-09-29"},{"url":"https://doi.org/10.1111/j.1464-5491.2004.01319.x","title":"Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial","publisher":"Diabetic Medicine","date":"2004-11","accessed":"2026-09-29"},{"url":"https://doi.org/10.2337/diacare.26.3.784","title":"Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial","publisher":"Diabetes Care","date":"2003-03","accessed":"2026-09-29"},{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff","title":"SYMLIN (pramlintide acetate) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: AstraZeneca)","date":"2019-12-18","accessed":"2026-09-29"},{"url":"https://doi.org/10.2337/dc08-0029","title":"Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity","publisher":"Diabetes Care","date":"2008-09","accessed":"2026-09-29"},{"url":"https://doi.org/10.1210/jc.2006-2003","title":"Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study","publisher":"Journal of Clinical Endocrinology & Metabolism","date":"2007-08","accessed":"2026-09-29"},{"url":"https://doi.org/10.2165/00063030-200317010-00008","title":"Pramlintide: (AC 137, AC 0137, Symlin, Tripro-Amylin)","publisher":"BioDrugs (Adis R&D profile)","date":"2003","accessed":"2026-09-29"},{"url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021332","title":"Drugs@FDA: SYMLIN (pramlintide acetate), NDA 021332","publisher":"U.S. Food and Drug Administration","date":"2026-09-29","accessed":"2026-09-29"}],"label":"Approved"},"route":"Subcutaneous injection at major meals, given as an add-on to mealtime insulin (US label: pen injector). Not taken by mouth.","halfLife":{"value":"About 48 minutes in healthy people (peak blood level after about 20 minutes)","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff","title":"SYMLIN (pramlintide acetate) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: AstraZeneca)","date":"2019-12-18","accessed":"2026-09-29"}},"structure":{"pubchemCid":70691388,"pdb":[{"id":"8F2B","description":"Cryo-EM structure (2.0 Å) of the human amylin 3 receptor (calcitonin receptor with RAMP3) bound to Gs and San45, an engineered analogue of pramlintide (Asn21 replaced by Lys). Shows how a pramlintide-like peptide sits in the amylin receptor. It is an analogue, not pramlintide itself."},{"id":"8F0K","description":"Cryo-EM structure (1.9 Å) of the human amylin 3 receptor bound to Gs and San385, another engineered pramlintide analogue (Ser19 replaced by Lys). An analogue, not pramlintide itself."},{"id":"8F0J","description":"Cryo-EM structure (2.0 Å) of the calcitonin receptor (without RAMP) bound to Gs and San45, the pramlintide analogue. Used to compare amylin-receptor and calcitonin-receptor recognition."}]},"companies":["astrazeneca"],"keyFacts":[{"label":"US approval","value":"FDA approved Symlin on 16 March 2005 (NDA 021332, new molecular entity); Drugs@FDA lists all Symlin products as Discontinued","source":{"url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021332","title":"Drugs@FDA: SYMLIN (pramlintide acetate), NDA 021332","publisher":"U.S. Food and Drug Administration","date":"2026-09-29","accessed":"2026-09-29"}},{"label":"Indication (US)","value":"Adjunct treatment in type 1 or type 2 diabetes for people using mealtime insulin who have not reached glycaemic control despite optimal insulin therapy","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff","title":"SYMLIN (pramlintide acetate) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: AstraZeneca)","date":"2019-12-18","accessed":"2026-09-29"}},{"label":"Structure","value":"37-amino-acid analogue of human amylin with proline substitutions at positions 25, 28 and 29; molecular weight 3949.4","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff","title":"SYMLIN (pramlintide acetate) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: AstraZeneca)","date":"2019-12-18","accessed":"2026-09-29"}},{"label":"Half-life and bioavailability","value":"About 48 minutes in healthy people; absolute bioavailability about 30-40% after subcutaneous injection","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff","title":"SYMLIN (pramlintide acetate) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: AstraZeneca)","date":"2019-12-18","accessed":"2026-09-29"}},{"label":"Type 1 diabetes, 52-week trial (n=651)","value":"HbA1c fell 0.29% and 0.34% from baseline with the two regimens reported (three or four times daily) vs 0.04% with placebo; weight -0.4 kg vs +0.8 kg","source":{"url":"https://doi.org/10.1111/j.1464-5491.2004.01319.x","title":"Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial","publisher":"Diabetic Medicine","date":"2004-11","accessed":"2026-09-29"}},{"label":"Type 2 diabetes, 52-week trial (n=656)","value":"HbA1c fell 0.62% from baseline at week 52 with the highest regimen, significantly more than with placebo (P<0.05); weight -1.4 kg vs +0.7 kg on placebo","source":{"url":"https://doi.org/10.2337/diacare.26.3.784","title":"Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial","publisher":"Diabetes Care","date":"2003-03","accessed":"2026-09-29"}}],"safety":[{"text":"Boxed warning: Symlin use with insulin increases the risk of severe hypoglycaemia, particularly in people with type 1 diabetes.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff","title":"SYMLIN (pramlintide acetate) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: AstraZeneca)","date":"2019-12-18","accessed":"2026-09-29"}},{"text":"Contraindicated in people with serious hypersensitivity to Symlin or its components, hypoglycaemia unawareness, or confirmed gastroparesis.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff","title":"SYMLIN (pramlintide acetate) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: AstraZeneca)","date":"2019-12-18","accessed":"2026-09-29"}},{"text":"Most common adverse effects in label trials were gastrointestinal: nausea in 48% (type 1) and 28% (type 2) of people vs 17% and 12% on placebo; anorexia 17% vs 2% (type 1) and 9% vs 2% (type 2).","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff","title":"SYMLIN (pramlintide acetate) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: AstraZeneca)","date":"2019-12-18","accessed":"2026-09-29"}},{"text":"Safety and effectiveness in pediatric patients have not been established.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff","title":"SYMLIN (pramlintide acetate) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: AstraZeneca)","date":"2019-12-18","accessed":"2026-09-29"}},{"text":"Pregnancy: the small number of reports in the manufacturer's safety database is not enough to determine a drug-associated risk of birth defects, miscarriage or other outcomes.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff","title":"SYMLIN (pramlintide acetate) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: AstraZeneca)","date":"2019-12-18","accessed":"2026-09-29"}},{"text":"Weight-loss use is unapproved. In a 4-month obesity study, nausea was the most common adverse event (9-29% with pramlintide vs 2% with placebo).","source":{"url":"https://doi.org/10.2337/dc08-0029","title":"Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity","publisher":"Diabetes Care","date":"2008-09","accessed":"2026-09-29"}}],"related":["cagrilintide","amycretin","eloralintide"],"lastVerified":"2026-09-29"},{"slug":"retatrutide","name":"Retatrutide","url":"https://glp1base.com/molecules/retatrutide","aliases":["LY3437943","LY-3437943"],"brands":[],"class":"incretin-pipeline","classLabel":"In clinical trials","targets":["GIP receptor","GLP-1 receptor","Glucagon receptor"],"summarySimple":"Retatrutide is an experimental once-a-week injection from Eli Lilly. It copies three natural gut and body hormones at once (GIP, GLP-1 and glucagon). In large trials, people lost a lot of weight, but it is not approved anywhere yet. Lilly says it plans to ask the US FDA for approval in early 2027.","summaryExpert":"Retatrutide (LY3437943) is an investigational, once-weekly, subcutaneously administered single-peptide agonist of the GIP, GLP-1 and glucagon receptors (GIPR, GLP-1R, GCGR). It is a 39-residue synthetic peptide (about 4.73 kDa) with three non-proteinogenic residues (Aib at positions 2 and 20, alpha-methyl-leucine at position 13), a C-terminal amide, and a C20 fatty diacid attached to Lys17 through a linker. In vitro it shows balanced GCGR and GLP-1R activity with relatively more GIPR activity (Coskun 2022). In a phase 1b multiple-ascending-dose study in type 2 diabetes, exposure was dose-proportional and the half-life was about 6 days, supporting weekly dosing. Phase 2 trials in obesity (NEJM 2023, NCT04881760) and type 2 diabetes (Lancet 2023, NCT04867785) showed dose-dependent weight and HbA1c reductions; the obesity trial reported a 24.2% mean weight reduction at 48 weeks in the highest-dose group versus 2.1% with placebo. The phase 3 TRIUMPH programme reported topline results in TRIUMPH-4 (knee osteoarthritis, December 2025), TRIUMPH-1 (obesity, May 2026, 2,339 participants, up to 28.3% mean weight loss at 80 weeks on the efficacy estimand versus 2.2% with placebo) and TRIUMPH-2 and TRIUMPH-3 (July 2026). TRANSCEND-T2D-1, a 40-week phase 3 monotherapy trial in type 2 diabetes, has been peer-reviewed (Lancet 2026). Common adverse events are gastrointestinal (nausea, diarrhoea, constipation, vomiting); dysesthesia has emerged as a notable dose-related signal in phase 3. Retatrutide is not approved by any regulator. Lilly says it plans a US Biologics License Application in Q1 2027; whether FDA treats it as a biologic (BLA) or a drug (NDA) has been disputed in court because of how amino acids in the molecule are counted. Outside clinical trials and a limited expanded-access programme it has no lawful supply, and products sold online as retatrutide are unapproved.","evidence":{"level":"phase3","note":"Not approved by any regulator. Evidence comes from Lilly-sponsored trials: phase 1 (single and multiple ascending dose), two published phase 2 trials (obesity, n=338; type 2 diabetes, n=281), a phase 2a liver-fat sub-study, one peer-reviewed phase 3 trial (TRANSCEND-T2D-1, n=537, 40 weeks) and industry topline press releases from the phase 3 TRIUMPH programme (TRIUMPH-4, -1, -2, -3). The TRIUMPH-1, -2, -3 and -4 figures are company-reported topline results that had not been peer-reviewed as of 2026-09-29. No dedicated cardiovascular outcomes result has been reported (in TRIUMPH-3, Lilly reported that major adverse cardiovascular events occurred less often than anticipated in both the retatrutide and placebo arms; the pre-specified hazard ratio for a five-component composite was 0.82, 95% CI 0.55 to 1.22, a range that does not exclude no effect). Lilly plans a US filing in Q1 2027. Preclinical work (mice, rats, hamsters) is used only for mechanism and is labelled animal-only below.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/37366315/","title":"Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial","publisher":"New England Journal of Medicine (PubMed)","date":"2023-08-10","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37385280/","title":"Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA","publisher":"The Lancet (PubMed)","date":"2023-08-12","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42250575/","title":"Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial","publisher":"The Lancet (PubMed)","date":"2026-06-13","accessed":"2026-09-29"},{"url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss-in-pivotal-phase-3-obesity-trial-302778859.html","title":"Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1 topline)","publisher":"Eli Lilly and Company (PR Newswire)","date":"2026-05-21","accessed":"2026-09-29"},{"url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html","title":"Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials (TRIUMPH-2 and TRIUMPH-3 topline)","publisher":"Eli Lilly and Company (PR Newswire)","date":"2026-07-23","accessed":"2026-09-29"},{"url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-weight-loss-of-up-to-an-average-of-71-2-lbs-along-with-substantial-relief-from-osteoarthritis-pain-in-first-successful-phase-3-trial-302638804.html","title":"Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial (TRIUMPH-4 topline)","publisher":"Eli Lilly and Company (PR Newswire)","date":"2025-12-11","accessed":"2026-09-29"},{"url":"https://www.biospace.com/fda/lilly-fda-retatrutide-biologic-dispute-comes-to-a-head-as-submission-nears","title":"Lilly, FDA retatrutide biologic dispute comes to a head as submission nears","publisher":"BioSpace","date":"2026-08-05","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT05929066","title":"A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight","publisher":"ClinicalTrials.gov, U.S. National Library of Medicine","date":"2023-07","accessed":"2026-09-29"},{"url":"https://clinicaltrials.gov/study/NCT07629401","title":"Pre-approval Expanded Access of Retatrutide (LY3437943)","publisher":"ClinicalTrials.gov, U.S. National Library of Medicine","date":"2026-06","accessed":"2026-09-29"}],"label":"Phase 3 trials"},"route":"Investigational. In clinical trials it is given by subcutaneous injection once a week. It has no approved route because it is not approved anywhere. Lilly's May 2026 release described it as legally available only to participants in Lilly's clinical trials. Since June 2026 Lilly has also listed a pre-approval, single-patient expanded-access programme, requested by a treating physician, for a narrow group of adults with severe obesity who cannot join a trial.","halfLife":{"value":"About 6 days (phase 1b study in type 2 diabetes)","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/36354040/","title":"LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial","publisher":"The Lancet (PubMed)","date":"2022-11-26","accessed":"2026-09-29"}},"structure":{"pubchemCid":171390338,"pdb":[{"id":"8YW3","description":"Cryo-EM structure (2.68 A) of retatrutide bound to the human GLP-1 receptor in complex with Gs protein. Released 2024-09-18 (Cell Discovery, 2024)."},{"id":"8YW4","description":"Cryo-EM structure (3.26 A) of retatrutide bound to the human GIP receptor in complex with Gs protein. Released 2024-09-18."},{"id":"8YW5","description":"Cryo-EM structure (2.84 A) of retatrutide bound to the human glucagon receptor in complex with Gs protein. Released 2024-08-07."}]},"companies":["eli-lilly"],"keyFacts":[{"label":"Regulatory status","value":"Not approved by any regulator as of 2026-09-29. Lilly says it plans to submit a Biologics License Application to the US FDA in Q1 2027. Lilly describes it as an investigational molecule that cannot be legally sold or marketed for human use.","source":{"url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html","title":"Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials (TRIUMPH-2 and TRIUMPH-3 topline)","publisher":"Eli Lilly and Company (PR Newswire)","date":"2026-07-23","accessed":"2026-09-29"}},{"label":"TRIUMPH-1 (obesity, 80 weeks)","value":"Highest dose: mean weight change -28.3% versus -2.2% with placebo (efficacy estimand); -25.0% versus -3.9% (treatment-regimen estimand). 2,339 randomised adults without diabetes. Company topline result, not yet peer-reviewed.","source":{"url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss-in-pivotal-phase-3-obesity-trial-302778859.html","title":"Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1 topline)","publisher":"Eli Lilly and Company (PR Newswire)","date":"2026-05-21","accessed":"2026-09-29"}},{"label":"TRIUMPH-1 extension (104 weeks)","value":"In a pre-specified extension of 532 participants with baseline BMI of 35 or more who completed the main study and tolerated their dose, mean weight change was -30.3% at 104 weeks in the group that continued the highest dose (a selected subgroup).","source":{"url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss-in-pivotal-phase-3-obesity-trial-302778859.html","title":"Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1 topline)","publisher":"Eli Lilly and Company (PR Newswire)","date":"2026-05-21","accessed":"2026-09-29"}},{"label":"TRIUMPH-2 and TRIUMPH-3 (80 weeks)","value":"Type 2 diabetes with obesity (n=1,152): up to -20.8% versus -4.0% placebo. Severe obesity with cardiovascular disease (n=1,949): up to -22.6% versus -3.2% placebo. Efficacy estimand, company topline results.","source":{"url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html","title":"Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials (TRIUMPH-2 and TRIUMPH-3 topline)","publisher":"Eli Lilly and Company (PR Newswire)","date":"2026-07-23","accessed":"2026-09-29"}},{"label":"TRANSCEND-T2D-1 (peer-reviewed phase 3)","value":"537 adults with type 2 diabetes, 40 weeks: HbA1c change -1.69% to -1.94% versus -0.81% with placebo; weight change -11.5% to -15.3% versus -2.6% (treatment-regimen estimand).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42250575/","title":"Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial","publisher":"The Lancet (PubMed)","date":"2026-06-13","accessed":"2026-09-29"}},{"label":"Half-life","value":"About 6 days (phase 1b, type 2 diabetes)","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/36354040/","title":"LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial","publisher":"The Lancet (PubMed)","date":"2022-11-26","accessed":"2026-09-29"}}],"safety":[{"text":"In TRIUMPH-1 the most common adverse events were gastrointestinal. At the highest dose versus placebo: nausea 42.4% vs 14.8%, diarrhoea 32.0% vs 13.5%, vomiting 25.3% vs 4.8%, constipation 26.1% vs 10.9%. Dysesthesia (abnormal skin sensations such as tingling or altered touch) was reported in 12.5% vs 0.9%, and urinary tract infections in 8.4% vs 5.3%. Discontinuation due to adverse events was 11.3% at the highest dose versus 4.9% with placebo. Retatrutide has no approved label, so there is no boxed warning or official safety statement yet.","source":{"url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss-in-pivotal-phase-3-obesity-trial-302778859.html","title":"Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1 topline)","publisher":"Eli Lilly and Company (PR Newswire)","date":"2026-05-21","accessed":"2026-09-29"}},{"text":"In TRIUMPH-4 (knee osteoarthritis), dysesthesia (abnormal skin sensations such as tingling or altered touch) was reported in 8.8% and 20.9% of people on the two retatrutide doses versus 0.7% with placebo. Lilly described these events as generally mild and said they rarely led to stopping treatment. In TRIUMPH-4 (knee osteoarthritis), discontinuation due to adverse events was 18.2% at the highest dose versus 4.0% with placebo; Lilly said these rates correlated with baseline BMI and included stopping for perceived excessive weight loss.","source":{"url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-weight-loss-of-up-to-an-average-of-71-2-lbs-along-with-substantial-relief-from-osteoarthritis-pain-in-first-successful-phase-3-trial-302638804.html","title":"Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial (TRIUMPH-4 topline)","publisher":"Eli Lilly and Company (PR Newswire)","date":"2025-12-11","accessed":"2026-09-29"}},{"text":"The phase 2 obesity trial reported dose-dependent increases in heart rate that peaked at 24 weeks and declined thereafter, and gastrointestinal events that were dose-related and mostly mild to moderate.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/37366315/","title":"Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial","publisher":"New England Journal of Medicine (PubMed)","date":"2023-08-10","accessed":"2026-09-29"}},{"text":"In a warning letter dated 2026-03-31 to a firm whose products included retatrutide, FDA stated that the products were unapproved new drugs. It said that, despite 'Research Use Only' and 'not intended for human consumption' labelling, evidence from the firm's website showed the products were intended as drugs, and noted that injectable products bypass some of the body's key defences against toxins and microorganisms.","source":{"url":"https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/gram-peptides-721806-03312026","title":"Gram Peptides, warning letter 721806","publisher":"U.S. Food and Drug Administration","date":"2026-03-31","accessed":"2026-09-29"}},{"text":"Australia's TGA warns that many peptide products supplied in Australia are unapproved, have not been assessed by the TGA for safety, quality or effectiveness, may not meet required standards and may be incorrectly labelled. This release is about unapproved peptides in general and does not name retatrutide.","source":{"url":"https://www.tga.gov.au/news/media-releases/tga-strengthens-compliance-focus-unapproved-peptide-products-part-evolving-risk-response","title":"TGA strengthens compliance focus on unapproved peptide products as part of evolving risk response","publisher":"Therapeutic Goods Administration (Australia)","date":"2026-06-10","accessed":"2026-09-29"}},{"text":"A 2026 case report described a man with type 1 diabetes who developed ketosis and acute kidney injury after using an online-purchased product marketed as retatrutide. The author states that causation cannot be established: stool culture also grew Shigella, and he had omitted insulin while unwell.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42669023/","title":"Online-Sourced Retatrutide Complicating Impending Diabetic Ketoacidosis in a Patient With Type 1 Diabetes and Concurrent Shigella Gastroenteritis","publisher":"Cureus (PubMed)","date":"2026-08-26","accessed":"2026-09-29"}}],"related":["tirzepatide","semaglutide","survodutide","mazdutide","orforglipron"],"lastVerified":"2026-09-29"},{"slug":"selank","name":"Selank","url":"https://glp1base.com/molecules/selank","aliases":["TP-7","Selanc","Thr-Lys-Pro-Arg-Pro-Gly-Pro","Threonyl-lysyl-prolyl-arginyl-prolyl-glycyl-proline","Tuftsin analogue heptapeptide"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["GABA-A receptor (positive allosteric modulation reported in rat brain membranes; not confirmed in humans)","Enkephalin-degrading enzymes in blood plasma (inhibition shown in vitro)","Exact receptor unknown; a receptor for Selank has not been identified"],"summarySimple":"Selank is a short chain of seven amino acids, built from a natural immune-system fragment called tuftsin. In Russia it is a registered nasal drop for anxiety. The FDA has not approved it, and no approval by other major regulators was found. Human studies are few, small and mostly in Russian, and most of how it might work comes from animal and lab tests.","summaryExpert":"Selank (TP-7) is a synthetic linear heptapeptide, Thr-Lys-Pro-Arg-Pro-Gly-Pro (C33H57N11O9, 751.9 Da), made by adding a Pro-Gly-Pro tail to the C-terminus of tuftsin (Thr-Lys-Pro-Arg, a fragment of the IgG heavy chain) to improve metabolic stability and prolong action; it was developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It is registered in the Russian Federation as Selank nasal drops (diacetate salt; ATC N05BX, held by Peptogen) for anxiety-spectrum conditions, and is used intranasally. The Russian label reports 92.8% nasal bioavailability, plasma detection within 30 seconds, plasma concentration falling over roughly 5 to 5.5 minutes, and no parent drug or metabolites in 24-hour urine because of rapid tissue peptidase degradation. No independent pharmacokinetic paper was found, so no formal half-life is given here. The mechanism is not established in humans. Preclinical and in vitro work reports inhibition of enkephalin-degrading enzymes in human plasma (IC50 15 microM), positive allosteric modulation of GABA-A binding in rat brain membranes, altered expression of GABAergic and inflammatory genes and of BDNF content in rodents, and cytokine changes in patient blood samples; a receptor has not been identified. Human efficacy evidence is limited to small, mostly open or comparator-controlled Russian studies (for example 62 patients with generalized anxiety disorder or neurasthenia compared with medazepam, and 60 patients compared with phenazepam). No placebo-controlled trial published in a major international journal was found, and no approval outside Russia was found in the sources checked. The FDA lists selank acetate among compounding nominations that were withdrawn and states it lacks important safety information for administration to humans. Use in any indication or country outside the Russian registration is unapproved.","evidence":{"level":"human-small","note":"Human data are small, mostly Russian-language clinical studies: a 62-patient comparison with medazepam in generalized anxiety disorder and neurasthenia, a 60-patient comparison with phenazepam, and a 70-patient study comparing Selank plus phenazepam with phenazepam alone. These used psychometric scales but were not, as far as the abstracts state, placebo-controlled, and no independent replication outside Russia was found. Mechanism evidence is mostly animal (rats and mice) and in vitro (rat brain membranes, cell lines, human blood samples). Selank is registered in Russia. It is not FDA-approved, and no approval by other major regulators was found in the sources checked. Any use outside the Russian label is unapproved.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/18454096/","title":"Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia (Zozulia et al.)","publisher":"Zh Nevrol Psikhiatr Im S S Korsakova (via PubMed)","date":"2008","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25176261/","title":"A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders (Medvedev et al.)","publisher":"Zh Nevrol Psikhiatr Im S S Korsakova (via PubMed)","date":"2014","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26356395/","title":"Optimization of the treatment of anxiety disorders with selank (Medvedev et al.)","publisher":"Zh Nevrol Psikhiatr Im S S Korsakova (via PubMed)","date":"2015","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34396551/","title":"Sedative-Hypnotic Agents That Impact Gamma-Aminobutyric Acid Receptors: Focus on Flunitrazepam, Gamma-Hydroxybutyric Acid, Phenibut, and Selank (Doyno et al.)","publisher":"J Clin Pharmacol (via PubMed)","date":"2021-08","accessed":"2026-09-29"}],"label":"Small human studies"},"route":"In its Russian registration Selank is given as nasal drops (intranasal); the Vidal drug reference lists it as a non-prescription medicine. Laboratory studies in rodents have used intranasal and intraperitoneal administration. The only registered form found is the nasal drop; no oral or injectable form was found in any registration checked, and this page gives no usage instructions.","halfLife":null,"structure":{"pubchemCid":11765600,"pdb":[]},"companies":[],"keyFacts":[{"label":"Status in Russia","value":"Registered in the Russian Federation as Selank 0.15% nasal drops (registration ЛП-№(010951)-(РГ-RU), dated 2025-07-15; previous registration ЛСР-003338/09); registrant Peptogen; listed by Vidal as non-prescription. Label indications are anxiety states (including panic attacks), neurasthenia, asthenia, sleep and mood disturbances, and adjustment disorders.","source":{"url":"https://www.vidal.ru/drugs/selank__21568","title":"Selank (Selank) nasal drops 0.15%: instructions for use (Vidal Russia drug reference, registration ЛП-№(010951)-(РГ-RU))","publisher":"Vidal (Russian drug reference; registrant Peptogen)","date":"2025-07-15","accessed":"2026-09-29"}},{"label":"Status in the US","value":"Not FDA-approved. FDA's safety-risk page (dated 2026-04-22) lists selank acetate (TP-7) among bulk substances whose nominations were withdrawn, and says compounded selank acetate may pose immunogenicity risk and that FDA lacks important safety information for administration to humans.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}},{"label":"July 2026 FDA advisory committee","value":"Selank was not among the peptides on the agenda of the 23-24 July 2026 Pharmacy Compounding Advisory Committee meeting (agenda: BPC-157, KPV, TB-500, MOTS-c, emideltide/DSIP, semax, epitalon).","source":{"url":"https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026","title":"July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee","publisher":"U.S. Food and Drug Administration","date":"2026-07-23","accessed":"2026-09-29"}},{"label":"Structure and mass","value":"Thr-Lys-Pro-Arg-Pro-Gly-Pro; C33H57N11O9; 751.9 g/mol (free peptide). It is tuftsin (Thr-Lys-Pro-Arg) extended by Pro-Gly-Pro.","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/11765600","title":"Selank (CID 11765600)","publisher":"PubChem, National Library of Medicine","date":"2026","accessed":"2026-09-29"}},{"label":"Selank vs another anxiolytic (small study)","value":"62 patients with generalized anxiety disorder and neurasthenia: Selank (30 patients) vs medazepam (32 patients); anxiolytic effects were reported as similar.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/18454096/","title":"Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia (Zozulia et al.)","publisher":"Zh Nevrol Psikhiatr Im S S Korsakova (via PubMed)","date":"2008","accessed":"2026-09-29"}},{"label":"Reported plasma behaviour (Russian label)","value":"Absolute nasal bioavailability 92.8%; detected in plasma at 30 seconds; plasma concentration declines over 5 to 5.5 minutes; no parent drug or metabolites in 24-hour urine.","source":{"url":"https://www.vidal.ru/drugs/selank__21568","title":"Selank (Selank) nasal drops 0.15%: indications, contraindications, pharmacokinetics (Vidal Russia drug reference, reproducing the Russian label)","publisher":"Vidal (Russian drug reference; registrant Peptogen)","date":"2018-10-22","accessed":"2026-09-29"}}],"safety":[{"text":"The Russian label lists only allergic reactions with individual intolerance and an unpleasant taste (when the drops reach the throat) as possible adverse effects. Contraindications are pregnancy, breastfeeding, age under 18 and hypersensitivity to the active substance.","source":{"url":"https://www.vidal.ru/drugs/selank__21568","title":"Selank (Selank) nasal drops 0.15%: indications, contraindications, pharmacokinetics (Vidal Russia drug reference, reproducing the Russian label)","publisher":"Vidal (Russian drug reference; registrant Peptogen)","date":"2018-10-22","accessed":"2026-09-29"}},{"text":"FDA states that compounded drugs containing selank acetate may pose a risk of immunogenicity for certain routes of administration because of the potential for aggregation and peptide-related impurities, and that FDA lacks important information about safety issues raised by selank acetate administered to humans.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}},{"text":"A 2021 review in a clinical pharmacology journal describes Selank, together with phenibut, as poorly studied Russian drugs with GABA-related mechanisms that are sold to US consumers as dietary supplements. It says new agents with GABA-related properties should be evaluated for abuse potential before public access.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/34396551/","title":"Sedative-Hypnotic Agents That Impact Gamma-Aminobutyric Acid Receptors: Focus on Flunitrazepam, Gamma-Hydroxybutyric Acid, Phenibut, and Selank (Doyno et al.)","publisher":"J Clin Pharmacol (via PubMed)","date":"2021-08","accessed":"2026-09-29"}},{"text":"Analysts of seized pharmaceutical preparations found unknown products that contained Selank and Semax, and noted that such peptides were being sold online outside regulated medicine channels, so the content and purity of unregulated products cannot be assumed.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/31667971/","title":"The occurrence of putative cognitive enhancing research peptides in seized pharmaceutical preparations: An incentive for controlling agencies to prepare for future encounters of the kind","publisher":"Drug Test Anal (via PubMed)","date":"2020-03","accessed":"2026-09-29"}},{"text":"No long-term safety study was found. The Russian clinical studies found in PubMed are small (60 to 70 patients) and were not designed as large safety studies.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/26356395/","title":"Optimization of the treatment of anxiety disorders with selank (Medvedev et al.)","publisher":"Zh Nevrol Psikhiatr Im S S Korsakova (via PubMed)","date":"2015","accessed":"2026-09-29"}}],"related":["semax"],"lastVerified":"2026-09-29"},{"slug":"semaglutide","name":"Semaglutide","url":"https://glp1base.com/molecules/semaglutide","aliases":["NN9535","NNC 0113-0217"],"brands":[{"name":"Ozempic","company":"novo-nordisk","indication":"Type 2 diabetes; lowering the risk of major heart events in adults with type 2 diabetes (injection: those with established heart disease; tablets: those at high risk); lowering kidney-disease and heart-death risk in adults with type 2 diabetes and chronic kidney disease (injection only)"},{"name":"Wegovy","company":"novo-nordisk","indication":"Chronic weight management (injection from age 12; tablets in adults); lowering heart-event risk in adults with established heart disease and obesity or overweight (injection and tablets); noncirrhotic MASH with moderate to advanced fibrosis in adults (injection only, accelerated approval)"},{"name":"Rybelsus","company":"novo-nordisk","indication":"Type 2 diabetes; lowering the risk of major heart events in adults with type 2 diabetes at high risk (oral tablet)"}],"class":"glp1-approved","classLabel":"Approved GLP-1 medicine","targets":["GLP-1 receptor"],"summarySimple":"Semaglutide copies a gut hormone called GLP-1. It helps the pancreas release insulin when blood sugar is high, slows the stomach a little, and quiets hunger signals in the brain. A fatty side chain lets it stick to a blood protein, so it lasts about a week in the body. It is approved medicine.","summaryExpert":"Semaglutide is a GLP-1 receptor agonist: a 31-residue peptide analogue with 94% sequence homology to human GLP-1, with its peptide backbone made by yeast fermentation (C187H291N45O59, 4113.58 g/mol). Three changes drive its profile: Aib at position 8 (stabilises it against DPP-4), Arg at position 34 (so only one lipid attaches), and a C18 fatty diacid on Lys26 via a hydrophilic spacer, which binds albumin (>99% bound) and lowers renal clearance. Subcutaneous bioavailability is 89%, peak levels come 1 to 3 days after a dose, and the elimination half-life is about 1 week, with steady state after 4 to 5 weeks. Tablets are co-formulated with the absorption enhancer SNAC; the label estimates absolute bioavailability at about 0.4% to 1% for Rybelsus and 1% to 2% for Ozempic tablets. It is approved by the FDA and EMA (Ozempic and Rybelsus for type 2 diabetes; Wegovy for weight management, with FDA-approved cardiovascular risk reduction and, under accelerated approval, MASH). Key trials: SUSTAIN-6 (cardiovascular outcomes in type 2 diabetes), STEP 1 (weight), SELECT (cardiovascular outcomes without diabetes), FLOW (kidney outcomes) and ESSENCE (MASH).","evidence":{"level":"approved","note":"Approved by the FDA (Ozempic 2017, Rybelsus 2019, Wegovy 2021; MASH indication 2025; Wegovy tablet December 2025) and by the EMA (Ozempic 2018, Rybelsus 2020, Wegovy 2022). Evidence comes from large randomised, placebo-controlled phase 3 trials: SUSTAIN-6 (3,297 people with type 2 diabetes), STEP 1 (1,961 adults with overweight or obesity), SELECT (17,604 adults with heart disease and overweight or obesity, no diabetes), FLOW (3,533 people with type 2 diabetes and chronic kidney disease) and ESSENCE part 1 (800 people in the interim analysis). All were funded by Novo Nordisk.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/33567185/","title":"Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)","publisher":"New England Journal of Medicine (via PubMed)","date":"2021-03-18","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27633186/","title":"Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6)","publisher":"New England Journal of Medicine (via PubMed)","date":"2016-11-10","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37952131/","title":"Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)","publisher":"New England Journal of Medicine (via PubMed)","date":"2023-12-14","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38785209/","title":"Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW)","publisher":"New England Journal of Medicine (via PubMed)","date":"2024-07-11","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40305708/","title":"Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis (ESSENCE)","publisher":"New England Journal of Medicine (via PubMed)","date":"2025-06-05","accessed":"2026-09-29"},{"url":"https://api.fda.gov/drug/drugsfda.json?search=application_number:NDA209637","title":"Drugs@FDA record, NDA 209637 (Ozempic): original approval 2017-12-05","publisher":"U.S. Food and Drug Administration (openFDA Drugs@FDA)","date":"2017-12-05","accessed":"2026-09-29"},{"url":"https://api.fda.gov/drug/drugsfda.json?search=application_number:NDA213051","title":"Drugs@FDA record, NDA 213051 (Rybelsus): original approval 2019-09-20","publisher":"U.S. Food and Drug Administration (openFDA Drugs@FDA)","date":"2019-09-20","accessed":"2026-09-29"},{"url":"https://api.fda.gov/drug/drugsfda.json?search=application_number:NDA215256","title":"Drugs@FDA record, NDA 215256 (Wegovy): original approval 2021-06-04","publisher":"U.S. Food and Drug Administration (openFDA Drugs@FDA)","date":"2021-06-04","accessed":"2026-09-29"},{"url":"https://api.fda.gov/drug/drugsfda.json?search=application_number:NDA218316","title":"Drugs@FDA record, NDA 218316 (Wegovy tablets): original approval 2025-12-22","publisher":"U.S. Food and Drug Administration (openFDA Drugs@FDA)","date":"2025-12-22","accessed":"2026-09-29"},{"url":"https://www.prnewswire.com/news-releases/wegovy-approved-by-fda-for-the-treatment-of-adults-with-noncirrhotic-mash-with-moderate-to-advanced-liver-fibrosis-302531394.html","title":"Wegovy approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis","publisher":"Novo Nordisk (PR Newswire)","date":"2025-08-15","accessed":"2026-09-29"},{"url":"https://www.ema.europa.eu/en/medicines/human/EPAR/ozempic","title":"Ozempic: EPAR (European public assessment report)","publisher":"European Medicines Agency","date":"2026-08","accessed":"2026-09-29"},{"url":"https://www.ema.europa.eu/en/medicines/human/EPAR/rybelsus","title":"Rybelsus: EPAR (European public assessment report)","publisher":"European Medicines Agency","date":"2026-04","accessed":"2026-09-29"},{"url":"https://www.ema.europa.eu/en/medicines/human/EPAR/wegovy","title":"Wegovy: EPAR (European public assessment report)","publisher":"European Medicines Agency","date":"2026-09","accessed":"2026-09-29"},{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=27f15fac-7d98-4114-a2ec-92494a91da98","title":"RYBELSUS and OZEMPIC (semaglutide) tablets: prescribing information","publisher":"DailyMed (U.S. National Library of Medicine) / Novo Nordisk","date":"2026-01","accessed":"2026-09-29"}],"label":"Approved"},"route":"Approved as a once-weekly subcutaneous injection (Ozempic, Wegovy) or as a once-daily oral tablet co-formulated with SNAC (Rybelsus, Ozempic tablets, Wegovy tablets), prescribed and supervised by a clinician.","halfLife":{"value":"About 1 week (elimination half-life); the drug stays in the blood for about 5 weeks after the last injection","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=adec4fd2-6858-4c99-91d4-531f5f2a2d79","title":"OZEMPIC (semaglutide) injection: prescribing information","publisher":"DailyMed (U.S. National Library of Medicine) / Novo Nordisk","date":"2026-06","accessed":"2026-09-29"}},"structure":{"pubchemCid":56843331,"pdb":[{"id":"4ZGM","description":"Crystal structure (1.8 A) of the semaglutide peptide backbone bound to the extracellular domain of the GLP-1 receptor. The peptide is shown without its fatty diacid side chain."},{"id":"7KI0","description":"Cryo-EM structure (2.5 A) of full-length GLP-1 receptor bound to semaglutide and the Gs protein, showing the active, signalling-ready complex (Cell Reports, 2021)."}]},"companies":["novo-nordisk"],"keyFacts":[{"label":"FDA approval, Ozempic","value":"Original FDA approval on 5 December 2017 (injection, type 2 diabetes).","source":{"url":"https://api.fda.gov/drug/drugsfda.json?search=application_number:NDA209637","title":"Drugs@FDA record, NDA 209637 (Ozempic): original approval 2017-12-05","publisher":"U.S. Food and Drug Administration (openFDA Drugs@FDA)","date":"2017-12-05","accessed":"2026-09-29"}},{"label":"FDA approval, Wegovy","value":"Original FDA approval on 4 June 2021 (injection, chronic weight management).","source":{"url":"https://api.fda.gov/drug/drugsfda.json?search=application_number:NDA215256","title":"Drugs@FDA record, NDA 215256 (Wegovy): original approval 2021-06-04","publisher":"U.S. Food and Drug Administration (openFDA Drugs@FDA)","date":"2021-06-04","accessed":"2026-09-29"}},{"label":"FDA approval for MASH","value":"On 15 August 2025 the FDA granted Wegovy accelerated approval for noncirrhotic MASH with moderate to advanced liver fibrosis; a study to confirm clinical benefit is ongoing.","source":{"url":"https://www.prnewswire.com/news-releases/wegovy-approved-by-fda-for-the-treatment-of-adults-with-noncirrhotic-mash-with-moderate-to-advanced-liver-fibrosis-302531394.html","title":"Wegovy approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis","publisher":"Novo Nordisk (PR Newswire)","date":"2025-08-15","accessed":"2026-09-29"}},{"label":"EMA authorisation, Ozempic","value":"Authorised in the European Union on 8 February 2018 for type 2 diabetes.","source":{"url":"https://www.ema.europa.eu/en/medicines/human/EPAR/ozempic","title":"Ozempic: EPAR (European public assessment report)","publisher":"European Medicines Agency","date":"2026-08","accessed":"2026-09-29"}},{"label":"STEP 1 weight result","value":"Mean weight change at 68 weeks was -14.9% with semaglutide versus -2.4% with placebo (1,961 adults, plus lifestyle intervention).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/33567185/","title":"Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)","publisher":"New England Journal of Medicine (via PubMed)","date":"2021-03-18","accessed":"2026-09-29"}},{"label":"SELECT heart outcomes","value":"Major cardiovascular events occurred in 6.5% on semaglutide versus 8.0% on placebo (hazard ratio 0.80; 17,604 adults with heart disease and overweight or obesity, no diabetes).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/37952131/","title":"Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)","publisher":"New England Journal of Medicine (via PubMed)","date":"2023-12-14","accessed":"2026-09-29"}}],"safety":[{"text":"Boxed warning: in rodents semaglutide caused dose- and duration-dependent thyroid C-cell tumours at clinically relevant exposures. Whether it does so in humans is unknown. It is contraindicated in people with a personal or family history of medullary thyroid carcinoma or with MEN 2.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b","title":"WEGOVY (semaglutide) injection and tablets: prescribing information","publisher":"DailyMed (U.S. National Library of Medicine) / Novo Nordisk","date":"2026-06","accessed":"2026-09-29"}},{"text":"Gastrointestinal effects are the most common adverse reactions. In the pooled weight-management trials of Wegovy injection versus placebo, nausea occurred in 44% versus 16%, diarrhoea 30% versus 16%, vomiting 24% versus 6% and constipation 24% versus 11%.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b","title":"WEGOVY (semaglutide) injection and tablets: prescribing information","publisher":"DailyMed (U.S. National Library of Medicine) / Novo Nordisk","date":"2026-06","accessed":"2026-09-29"}},{"text":"The label warns of acute pancreatitis, acute gallbladder disease (cholelithiasis in 1.6% of adults on Wegovy injection versus 0.7% on placebo in weight-reduction trials), acute kidney injury from volume depletion, and hypersensitivity reactions.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b","title":"WEGOVY (semaglutide) injection and tablets: prescribing information","publisher":"DailyMed (U.S. National Library of Medicine) / Novo Nordisk","date":"2026-06","accessed":"2026-09-29"}},{"text":"In SUSTAIN-6, diabetic retinopathy complications were higher with semaglutide than placebo (hazard ratio 1.76; 95% CI 1.11 to 2.78) in people with type 2 diabetes at high cardiovascular risk.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/27633186/","title":"Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6)","publisher":"New England Journal of Medicine (via PubMed)","date":"2016-11-10","accessed":"2026-09-29"}},{"text":"Because semaglutide delays gastric emptying, there are rare post-marketing reports of pulmonary aspiration during general anaesthesia or deep sedation in people taking GLP-1 receptor agonists.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b","title":"WEGOVY (semaglutide) injection and tablets: prescribing information","publisher":"DailyMed (U.S. National Library of Medicine) / Novo Nordisk","date":"2026-06","accessed":"2026-09-29"}},{"text":"Compounded semaglutide products are not FDA-approved. As of 31 May 2026 the FDA had received 990 adverse-event reports associated with compounded semaglutide. The FDA notes these events are likely underreported, because federal law does not require state-licensed pharmacies that are not outsourcing facilities to report them.","source":{"url":"https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss","title":"FDA's concerns with unapproved GLP-1 drugs used for weight loss","publisher":"U.S. Food and Drug Administration","date":"2026-09-01","accessed":"2026-09-29"}}],"related":["liraglutide","tirzepatide","cagrilintide","dulaglutide","exenatide","orforglipron"],"lastVerified":"2026-09-29"},{"slug":"semax","name":"Semax","url":"https://glp1base.com/molecules/semax","aliases":["ACTH(4-7)PGP","ACTH(4-7)-Pro-Gly-Pro","MEHFPGP","Met-Glu-His-Phe-Pro-Gly-Pro","Semax acetate (salt form)"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["Not fully defined. Specific, saturable membrane binding sites have been described in rat basal forebrain tissue (dissociation constant about 2.4 nM), but the binding molecule has not been identified","BDNF/TrkB and NGF neurotrophin signalling (increased expression in rat brain; animal data)","Enkephalin-degrading peptidases (inhibited in vitro, in human serum; IC50 about 10 micromolar)"],"summarySimple":"Semax is a short chain of seven amino acids, built from a piece of a natural stress hormone called ACTH. It is a registered nasal-drop medicine in Russia, where it is used mainly to treat stroke. It is not approved by the US FDA, and no approval by other major regulators was found. Human studies are few, small and mostly in Russian, and most of the lab evidence is from rats.","summaryExpert":"Semax is a synthetic linear heptapeptide, H-Met-Glu-His-Phe-Pro-Gly-Pro-OH (C37H51N9O10S, 813.93 g/mol; CAS 80714-61-0; PubChem CID 9811102). It consists of the ACTH(4-7) fragment (Met-Glu-His-Phe) joined to a C-terminal Pro-Gly-Pro tripeptide that is thought to slow peptidase hydrolysis; it is often loosely described as an ACTH(4-10) analogue. It lacks the corticotropic (adrenal) and melanotropic activity of full-length ACTH but keeps neurobehavioural effects in rodents. Developed at the Institute of Molecular Genetics, Russian Academy of Sciences, it is registered in Russia as a nootropic/neuroprotective nasal-drop medicine in two strengths; it is not a component of any FDA-approved drug, no approval by the EMA, MHRA, PMDA, NMPA, TGA or Health Canada was identified in the sources checked, and it has no USP/NF, European, Japanese or International Pharmacopoeia monograph. Its mechanism is not established. In rodents it rapidly raises Bdnf, Ngf and TrkB expression, binds specific membrane sites in the basal forebrain, and alters serotonergic and dopaminergic signalling; it also shows anticoagulant/antithrombotic and analgesic effects in rodents, and inhibits enkephalin-degrading peptidases in vitro. After intranasal delivery to rats it reaches the brain within minutes but is degraded quickly, with Pro-Gly-Pro the main metabolite. FDA reviewers found no human pharmacokinetic data by any route. Clinical evidence consists of small, mostly Russian-language, open-label or non-blinded studies (for example ischemic stroke rehabilitation, cerebrovascular insufficiency, optic neuropathy, motor neuron disease, and one small fMRI study in healthy volunteers); no large randomised placebo-controlled trials were identified. In the US, semax was no longer in the FDA compounding 'Category 2' list by April 2026 (FDA lists its nomination as withdrawn), and on 24 July 2026, the second day of a two-day meeting, the FDA Pharmacy Compounding Advisory Committee voted 8-5 (1 abstention) to recommend adding it to the 503A bulks list, against the recommendation of FDA staff, who judged the evidence of effectiveness insufficient and the substance not well characterised. That vote is advisory only, and rulemaking has not been completed.","evidence":{"level":"human-small","note":"No approval from a major regulator. In Russia semax is a registered drug, and human data come from small, mostly Russian-language studies that are open-label, non-blinded or reported only as abstracts. Examples: 110 post-stroke patients followed for 5 months in subgroups with and without semax (plasma BDNF and Barthel index; the English abstract does not describe blinding or randomisation); 187 patients with cerebrovascular insufficiency; 27 patients with motor neuron disease in an open-label trial (no effect on disease course, some improvement in a quality-of-life score); and a resting-state fMRI study of 14 healthy adults on semax versus 10 on placebo. For the uses nominated in the US (cerebral ischemia, migraine and trigeminal neuralgia), FDA reviewers in 2026 found only two usable clinical references: a meeting abstract without clinical endpoints and one small, uncontrolled, open-label study. They did not assess the Russian-language stroke studies because no English translations were available, and they concluded there was insufficient evidence of effectiveness. Most mechanistic work is in rats and cell cultures (animal-only and cell-only).","sources":[{"url":"https://www.fda.gov/media/193348/download","title":"FDA Briefing Document for Semax-Related Bulk Drug Substances (Semax (free base) and Semax acetate), Pharmacy Compounding Advisory Committee meeting, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29798983/","title":"The efficacy of semax in the treatment of patients at different stages of ischemic stroke","publisher":"Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova (PubMed)","date":"2018","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15792140/","title":"Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency","publisher":"Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova (PubMed)","date":"2005","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18379501/","title":"The study of chronic partial denervation and quality of life in patients with motor neuron disease treated with semax","publisher":"Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova (PubMed)","date":"2007","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30225715/","title":"Effects of Semax on the Default Mode Network of the Brain","publisher":"Bulletin of Experimental Biology and Medicine (PubMed)","date":"2018-09","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10741256/","title":"Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease","publisher":"Vestnik Oftalmologii (PubMed)","date":"2000","accessed":"2026-09-29"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9030433/","title":"Development of Peptide Biopharmaceuticals in Russia","publisher":"Pharmaceutics (PubMed Central)","date":"2022-03-27","accessed":"2026-09-29"}],"label":"Small human studies"},"route":"In Russian clinical practice it is given as an intranasal solution (nasal drops), in two strengths. Published human studies have used the intranasal route almost exclusively; FDA reviewers found no human data for subcutaneous injection. This record describes how semax has been studied and registered in Russia, not how anyone should use it.","halfLife":null,"structure":{"pubchemCid":9811102,"pdb":[]},"companies":[],"keyFacts":[{"label":"Chemical identity","value":"Linear heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro; molecular formula C37H51N9O10S; molecular weight 813.93 g/mol (free base); the acetate salt is C39H55N9O12S, 874.0 g/mol","source":{"url":"https://www.fda.gov/media/193348/download","title":"FDA Briefing Document for Semax-Related Bulk Drug Substances (Semax (free base) and Semax acetate), Pharmacy Compounding Advisory Committee meeting, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05","accessed":"2026-09-29"}},{"label":"Where it is a registered medicine","value":"Registered in Russia as nasal drops in two strengths; FDA notes it is not a component of any FDA-approved drug and has no monograph in the European, Japanese or International Pharmacopoeias.","source":{"url":"https://www.fda.gov/media/193348/download","title":"FDA Briefing Document for Semax-Related Bulk Drug Substances (Semax (free base) and Semax acetate), Pharmacy Compounding Advisory Committee meeting, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05","accessed":"2026-09-29"}},{"label":"US compounding status (September 2026)","value":"On 24 July 2026 (day two of the 23-24 July meeting) the Pharmacy Compounding Advisory Committee voted 8-5 (1 abstention) to recommend adding semax (free base and acetate) to the 503A bulks list, after FDA staff recommended against. The vote is advisory, and adding a substance requires rulemaking that had not been completed in the sources checked","source":{"url":"https://www.mcdermottlaw.com/insights/bulk-list-bound-pcac-backs-majority-of-peptides-in-two-day-public-meeting/","title":"Bulk List Bound: PCAC Backs Majority of Peptides in Two-Day Public Meeting","publisher":"McDermott Will & Schulte","date":"2026-07-27","accessed":"2026-09-29"}},{"label":"Brain delivery in rats","value":"About 0.093% of an intranasal radiolabelled dose per gram of brain at 2 minutes, of which about 80% was intact semax and the rest metabolites; across the samples, Pro-Gly-Pro was the main breakdown product","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/16523722/","title":"Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration","publisher":"Bioorganicheskaia Khimiia (PubMed)","date":"2006-01","accessed":"2026-09-29"}},{"label":"Human pharmacokinetics","value":"FDA reviewers found no human pharmacokinetic studies for semax by any route of administration, so no human half-life is available","source":{"url":"https://www.fda.gov/media/193348/download","title":"FDA Briefing Document for Semax-Related Bulk Drug Substances (Semax (free base) and Semax acetate), Pharmacy Compounding Advisory Committee meeting, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05","accessed":"2026-09-29"}},{"label":"US compounding list history","value":"FDA's Category 2 page (updated April 2026) lists semax (heptapeptide) under substances previously in Category 2 whose nominations were withdrawn, so it is no longer in Category 2. Leaving Category 2 is not the same as being placed on the 503A bulks list","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04","accessed":"2026-09-29"}}],"safety":[{"text":"Human safety data are thin. FDA counted about 33-47 healthy adults, 69 adults with medical conditions and 451 children given intranasal semax across the published references it found; most references did not discuss adverse events, and several combined semax with other treatments. FDA concluded there is insufficient clinical information to characterise its safety profile.","source":{"url":"https://www.fda.gov/media/193348/download","title":"FDA Briefing Document for Semax-Related Bulk Drug Substances (Semax (free base) and Semax acetate), Pharmacy Compounding Advisory Committee meeting, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05","accessed":"2026-09-29"}},{"text":"Possible bleeding risk: rat studies point to anticoagulant/antithrombotic activity (a meeting abstract that included human subjects did not make clear whether its clotting tests were done in rats or people), and FDA flagged concern for people at risk of bleeding or taking other drugs that raise bleeding risk.","source":{"url":"https://www.fda.gov/media/193348/download","title":"FDA Briefing Document for Semax-Related Bulk Drug Substances (Semax (free base) and Semax acetate), Pharmacy Compounding Advisory Committee meeting, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05","accessed":"2026-09-29"}},{"text":"In mice, semax strongly increased amphetamine-induced dopamine release and movement in the striatum. FDA noted this pattern is typical of drugs of abuse and that no study of semax's abuse potential was found.","source":{"url":"https://www.fda.gov/media/193348/download","title":"FDA Briefing Document for Semax-Related Bulk Drug Substances (Semax (free base) and Semax acetate), Pharmacy Compounding Advisory Committee meeting, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05","accessed":"2026-09-29"}},{"text":"Unregulated products are poorly characterised. FDA found inconsistent naming (free base versus acetate salt), no public data on impurity limits, aggregates, endotoxin or microbial load, and raised immunogenicity concerns for injectable or nasal products made from unverified material.","source":{"url":"https://www.fda.gov/media/193348/download","title":"FDA Briefing Document for Semax-Related Bulk Drug Substances (Semax (free base) and Semax acetate), Pharmacy Compounding Advisory Committee meeting, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05","accessed":"2026-09-29"}},{"text":"Only one adverse-event report was found in FDA's FAERS database through 3 December 2025: a consumer reported eye pain and burning, with hospitalisation, after using a nasal product obtained online. A single report cannot show cause.","source":{"url":"https://www.fda.gov/media/193348/download","title":"FDA Briefing Document for Semax-Related Bulk Drug Substances (Semax (free base) and Semax acetate), Pharmacy Compounding Advisory Committee meeting, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05","accessed":"2026-09-29"}},{"text":"No repeat-dose toxicity, genotoxicity or reproductive-toxicity studies of semax were identified by FDA reviewers, so those risks are unstudied rather than shown to be absent.","source":{"url":"https://www.fda.gov/media/193348/download","title":"FDA Briefing Document for Semax-Related Bulk Drug Substances (Semax (free base) and Semax acetate), Pharmacy Compounding Advisory Committee meeting, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05","accessed":"2026-09-29"}}],"related":["selank","epitalon","melanotan-ii"],"lastVerified":"2026-09-29"},{"slug":"sermorelin","name":"Sermorelin","url":"https://glp1base.com/molecules/sermorelin","aliases":["Sermorelin acetate","GHRH(1-29)-NH2","GRF(1-29)-NH2","hGRF(1-29)-NH2","Geref (former US brand, withdrawn)"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["Growth hormone-releasing hormone (GHRH) receptor on pituitary somatotroph cells"],"summarySimple":"Sermorelin is a lab-made copy of the first 29 building blocks of a natural brain hormone that tells the pituitary gland to release growth hormone. The US once approved it as a test and for children with low growth hormone. The maker stopped selling it, and both US approvals were withdrawn in 2009. FDA said this was not for safety reasons.","summaryExpert":"Sermorelin is GHRH(1-29)-NH2, a 29-residue C-terminally amidated peptide (C149H246N44O42S, about 3358 Da) whose sequence is identical to the N-terminal 29 residues of human growth hormone-releasing hormone (GHRH 1-44); it is the shortest fragment that keeps the full biological activity of the parent hormone. It activates the GHRH receptor (a class B G protein-coupled receptor coupled to Gs) on pituitary somatotrophs, stimulating pulsatile GH release and, downstream, IGF-I, with the physiological feedback system (somatostatin) remaining in place. It has no engineered half-life extension: a Serono review attributes its short half-life mostly to renal ultrafiltration and N-terminal enzymatic degradation (plasma dipeptidyl-peptidase removal of Tyr-Ala was shown for GHRH 1-44), and its plasma half-life in humans is short, reported as about 10 to 20 minutes in a review, with a disappearance half-time of 4.3 min in an infusion study in ten men, yet GH stays raised for about 3 hours after an intravenous dose. Subcutaneous exposure was about 4% of intravenous in an anaesthetised-rat study (animal-only). Regulatory history (FDA): NDA 19-863 (diagnostic ampules, evaluation of pituitary GH secretory ability) was approved 1990-12-28 and NDA 20-443 (idiopathic GH deficiency in children with growth failure) on 1997-09-26, both held by EMD Serono. The company reported discontinuation in 2008 and requested withdrawal; approval of both NDAs was withdrawn effective 2009-06-18, and in 2013 FDA determined the products were not withdrawn for reasons of safety or effectiveness. Key evidence is an open-label, 110-child, one-year study (Geref International Study Group, 1996) and a 1999 review; mean height velocity rose from 4.1 to 8.0 cm/yr at 6 months and 7.2 cm/yr at 12 months in GH-deficient children. A 1999 review notes there was no direct comparison with somatropin, and that height-velocity gains with sermorelin given by continuous infusion or in three divided doses were smaller than with daily somatropin in other children; effect on final adult height was not established. Use in healthy adults, or for anti-ageing or body-composition aims, is unapproved and rests on small, short human studies. Compounding and country-by-country legal status are covered in the status records, not here.","evidence":{"level":"human-small","note":"Sermorelin has real human clinical data, but no current marketing authorisation. The best data are one open-label, uncontrolled 12-month study of 110 previously untreated children with growth hormone deficiency (Geref International Study Group, 1996), earlier small paediatric studies (for example, eight children in a 1990 continuous-infusion study), and a 1999 review that supported the former US approvals. In adults there are only small, short studies, such as a two-week crossover in old men that raised GH and IGF-I. No large randomised trial shows benefit for healthy adults, and none of the studies we reviewed reports final adult height; the 1999 review notes only a few children followed for up to 36 months. Its FDA approvals (1990 and 1997) were withdrawn in 2009 after the company stopped selling it.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/8772599/","title":"Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy (Geref International Study Group; J Clin Endocrinol Metab)","publisher":"PubMed / Journal of Clinical Endocrinology & Metabolism","date":"1996-03","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18031173/","title":"Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency (Prakash A, Goa KL; BioDrugs 12(2):139-157)","publisher":"PubMed / BioDrugs","date":"1999-08","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/1379256/","title":"Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men (Corpas E et al.; J Clin Endocrinol Metab)","publisher":"PubMed / Journal of Clinical Endocrinology & Metabolism","date":"1992-08","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/2140733/","title":"Continuous subcutaneous GHRH(1-29)NH2 promotes growth over 1 year in short, slowly growing children (Clinical Endocrinology)","publisher":"PubMed / Clinical Endocrinology","date":"1990-02","accessed":"2026-09-29"},{"url":"https://www.federalregister.gov/documents/2013/03/04/2013-04827/determination-that-geref-sermorelin-acetate-injection-05-milligrams-basevial-and-10-milligrams","title":"Determination That GEREF (Sermorelin Acetate) Injection, 0.5 mg Base/Vial and 1.0 mg Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 mg Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness","publisher":"U.S. Food and Drug Administration, Federal Register (78 FR 14095)","date":"2013-03-04","accessed":"2026-09-29"}],"label":"Small human studies"},"route":"When it was FDA-approved (Geref), it was given by injection: as a single intravenous test to check pituitary growth hormone reserve, and as a daily subcutaneous injection for children with idiopathic growth hormone deficiency under specialist care. It has also been studied in small trials by subcutaneous and intravenous routes and by continuous subcutaneous infusion; a nasal route was tested in healthy men and absorbed poorly (about 3 to 5% bioavailability). It is not approved for any other use.","halfLife":{"value":"Short: about 10 to 20 minutes in humans, according to a 2003 review by Serono scientists, mostly because the kidneys filter it out and enzymes cut its front end.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/14499707/","title":"PEGylation of growth hormone-releasing hormone (GRF) analogues (Advanced Drug Delivery Reviews)","publisher":"PubMed / Advanced Drug Delivery Reviews","date":"2003-09-26","accessed":"2026-09-29"}},"structure":{"pubchemCid":16132413,"pdb":[{"id":"7CZ5","description":"Cryo-EM structure (2.6 A resolution) of the human GHRH receptor bound to Gs protein and human GHRH(1-44). Sermorelin is residues 1 to 29 of this same hormone, so the structure shows how the natural hormone that sermorelin copies sits in its receptor. It is not sermorelin itself."}]},"companies":[],"keyFacts":[{"label":"FDA approvals (both withdrawn)","value":"NDA 19-863 (diagnostic ampules) approved 1990-12-28 and NDA 20-443 (children with idiopathic growth hormone deficiency) approved 1997-09-26; holder EMD Serono; brand Geref.","source":{"url":"https://www.federalregister.gov/documents/2013/03/04/2013-04827/determination-that-geref-sermorelin-acetate-injection-05-milligrams-basevial-and-10-milligrams","title":"Determination That GEREF (Sermorelin Acetate) Injection, 0.5 mg Base/Vial and 1.0 mg Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 mg Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness","publisher":"U.S. Food and Drug Administration, Federal Register (78 FR 14095)","date":"2013-03-04","accessed":"2026-09-29"}},{"label":"Approval withdrawn","value":"Approval of both NDAs was withdrawn effective 2009-06-18 after the company reported discontinuation in 2008. In 2013 FDA determined the products were not withdrawn from sale for reasons of safety or effectiveness.","source":{"url":"https://www.federalregister.gov/documents/2013/03/04/2013-04827/determination-that-geref-sermorelin-acetate-injection-05-milligrams-basevial-and-10-milligrams","title":"Determination That GEREF (Sermorelin Acetate) Injection, 0.5 mg Base/Vial and 1.0 mg Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 mg Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness","publisher":"U.S. Food and Drug Administration, Federal Register (78 FR 14095)","date":"2013-03-04","accessed":"2026-09-29"}},{"label":"Paediatric trial result","value":"In 110 previously untreated GH-deficient children (86 evaluable), height velocity rose from 4.1 to 8.0 cm/yr at 6 months and 7.2 cm/yr at 12 months; 74% were good responders at 6 months (open-label, no control group).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/8772599/","title":"Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy (Geref International Study Group; J Clin Endocrinol Metab)","publisher":"PubMed / Journal of Clinical Endocrinology & Metabolism","date":"1996-03","accessed":"2026-09-29"}},{"label":"Molecular size","value":"29 amino acids, C-terminal amide, formula C149H246N44O42S, molecular weight 3357.9.","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/16132413","title":"Sermorelin (PubChem CID 16132413)","publisher":"National Center for Biotechnology Information, PubChem","date":"2026","accessed":"2026-09-29"}},{"label":"Half-life","value":"Roughly 10 to 20 minutes in humans (2003 review).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/14499707/","title":"PEGylation of growth hormone-releasing hormone (GRF) analogues (Advanced Drug Delivery Reviews)","publisher":"PubMed / Advanced Drug Delivery Reviews","date":"2003-09-26","accessed":"2026-09-29"}},{"label":"Measured clearance in men","value":"Disappearance half-time of 4.3 +/- 1.4 min during and after a constant intravenous infusion in 10 healthy men.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/7962295/","title":"Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men (J Clin Endocrinol Metab)","publisher":"PubMed / Journal of Clinical Endocrinology & Metabolism","date":"1994-10","accessed":"2026-09-29"}},{"label":"FDA 503A bulk-substance categories","value":"Sermorelin does not appear in any of the three categories (under evaluation, significant safety risks, nominated without adequate support) in FDA's list of nominated bulk substances, last updated 2026-05-14. Compounding legality is covered in the country status records.","source":{"url":"https://www.fda.gov/media/94155/download","title":"Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (categories 1 to 3; updated May 14, 2026)","publisher":"U.S. Food and Drug Administration","date":"2026-05-14","accessed":"2026-09-29"}}],"safety":[{"text":"In clinical use in children and as a diagnostic test, sermorelin was reported to be well tolerated; transient facial flushing and pain at the injection site were the most commonly reported adverse events.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/18031173/","title":"Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency (Prakash A, Goa KL; BioDrugs 12(2):139-157)","publisher":"PubMed / BioDrugs","date":"1999-08","accessed":"2026-09-29"}},{"text":"In the 110-child one-year study, no adverse changes in general biochemical or hormonal tests were noted, there was no change in fasting glucose, and IGF-I did not rise excessively.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/8772599/","title":"Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy (Geref International Study Group; J Clin Endocrinol Metab)","publisher":"PubMed / Journal of Clinical Endocrinology & Metabolism","date":"1996-03","accessed":"2026-09-29"}},{"text":"Evidence in adults is small and short: in a 14-day crossover in old men, GHRH(1-29) did not change fasting glucose, urinary C-peptide, blood pressure, or chemistry and haematology profiles. Longer-term safety in healthy adults has not been established by the studies we reviewed.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/1379256/","title":"Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men (Corpas E et al.; J Clin Endocrinol Metab)","publisher":"PubMed / Journal of Clinical Endocrinology & Metabolism","date":"1992-08","accessed":"2026-09-29"}},{"text":"FDA determined in 2013 that Geref was not withdrawn from sale for reasons of safety or effectiveness; the withdrawal followed the manufacturer's decision to discontinue the product.","source":{"url":"https://www.federalregister.gov/documents/2013/03/04/2013-04827/determination-that-geref-sermorelin-acetate-injection-05-milligrams-basevial-and-10-milligrams","title":"Determination That GEREF (Sermorelin Acetate) Injection, 0.5 mg Base/Vial and 1.0 mg Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 mg Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness","publisher":"U.S. Food and Drug Administration, Federal Register (78 FR 14095)","date":"2013-03-04","accessed":"2026-09-29"}},{"text":"Sermorelin is not named on FDA's page of bulk substances that may present significant safety risks. For other peptides on that page, FDA cites immunogenicity from aggregation and peptide-related impurities as concerns, so the quality of unregulated or compounded peptide products is a general open question rather than a sermorelin-specific finding.","source":{"url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","title":"Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks","publisher":"U.S. Food and Drug Administration","date":"2026-04-22","accessed":"2026-09-29"}}],"related":["tesamorelin","cjc-1295","ipamorelin"],"lastVerified":"2026-09-29"},{"slug":"setmelanotide","name":"Setmelanotide","url":"https://glp1base.com/molecules/setmelanotide","aliases":["RM-493","BIM-22493","Acetyl-Arg-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys-NH2 (cyclic disulfide)"],"brands":[{"name":"Imcivree","company":"rhythm-pharmaceuticals","indication":"Reduce excess body weight and maintain the reduction in acquired hypothalamic obesity (age 4+), Bardet-Biedl syndrome (age 2+) and POMC, PCSK1 or LEPR deficiency confirmed by genetic testing (age 2+) (US label)"}],"class":"peptide-approved","classLabel":"Approved peptide medicine","targets":["Melanocortin-4 receptor (MC4R) agonist; about 20-fold less active at MC3R and MC1R"],"summarySimple":"Setmelanotide is a small protein-like medicine for rare kinds of obesity where the brain's hunger-control system is broken, by a gene fault or by damage to the hypothalamus. It switches on the melanocortin-4 receptor, which tells the brain you are full. It is given as a daily injection and is not for common obesity.","summaryExpert":"Setmelanotide is a synthetic cyclic octapeptide, acetyl-Arg-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys-NH2 with a Cys2-Cys8 disulfide (C49H68N18O9S2, 1117.3 Da), built around the core melanocortin pharmacophore His-D-Phe-Arg-Trp. The D-amino acids, N-terminal acetylation and C-terminal amide are stabilising modifications. It is an agonist of the melanocortin-4 receptor (MC4R) with about 20-fold less activity at MC3R and MC1R (US label); MC4R signalling in the hypothalamus regulates hunger, satiety and energy expenditure, and setmelanotide acts downstream of the leptin-POMC step that is defective in POMC, PCSK1 and LEPR deficiency. After subcutaneous injection the median Tmax is about 8 hours, apparent volume of distribution 75.2 L, plasma protein binding 79.1%, about 39% is excreted unchanged in urine over a dosing interval, and the half-life is about 11 hours, consistent with once-daily use. The FDA approved it on 27 November 2020 for POMC, PCSK1 or LEPR deficiency (single-arm phase 3 trials in 10 and 11 people), later added Bardet-Biedl syndrome, and on 19 March 2026 added acquired hypothalamic obesity (age 4+) on the basis of the randomised phase 3 TRANSCEND trial (NEJM 2026). The EU authorised it in July 2021 and now lists the same three indication groups. The US label has no boxed warning; warnings cover depression and suicidal ideation, hypersensitivity including anaphylaxis, skin hyperpigmentation and nevi, sexual arousal disturbances, and (in acquired hypothalamic obesity) adrenal insufficiency and sodium imbalance. It is not approved for common polygenic obesity.","evidence":{"level":"approved","note":"Approved by the US FDA (2020, expanded since) and the European Commission (2021, expanded since) for narrowly defined rare conditions. Evidence is one randomised placebo-controlled phase 3 trial in acquired hypothalamic obesity (TRANSCEND; the NEJM paper reports 120 randomised participants, while the current US label and the company's press release report 142 randomised patients with a placebo-adjusted BMI difference of -18.4%; the sources checked do not explain the difference, so the trial figures in this record are the NEJM ones), a randomised phase 3 trial in Bardet-Biedl and Alstrom syndromes (38 patients), and two very small single-arm phase 3 trials in POMC/PCSK1 and LEPR deficiency (10 and 11 people). Use in other types of obesity is unapproved.","sources":[{"url":"https://doi.org/10.1056/NEJMoa2512275","title":"Setmelanotide for the Treatment of Acquired Hypothalamic Obesity","publisher":"New England Journal of Medicine","date":"2026-07-09","accessed":"2026-09-29"},{"url":"https://doi.org/10.1016/S2213-8587(22)00277-7","title":"Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alstrom syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period","publisher":"The Lancet Diabetes & Endocrinology","date":"2022-12","accessed":"2026-09-29"},{"url":"https://doi.org/10.1016/S2213-8587(20)30364-8","title":"Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials","publisher":"The Lancet Diabetes & Endocrinology","date":"2020-12","accessed":"2026-09-29"},{"url":"https://doi.org/10.1056/NEJMoa1512693","title":"Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist","publisher":"New England Journal of Medicine","date":"2016-07-21","accessed":"2026-09-29"},{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9","title":"IMCIVREE (setmelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Rhythm Pharmaceuticals)","date":"2026-04-01","accessed":"2026-09-29"}],"label":"Approved"},"route":"Subcutaneous injection, given once daily in approved use (US and EU labels). Not given by mouth, intravenously or into muscle.","halfLife":{"value":"About 11 hours (median time to peak about 8 hours after subcutaneous injection)","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9","title":"IMCIVREE (setmelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Rhythm Pharmaceuticals)","date":"2026-04-01","accessed":"2026-09-29"}},"structure":{"pubchemCid":11993702,"pdb":[{"id":"7PIU","description":"Cryo-EM structure (2.6 A) of setmelanotide bound to the active human melanocortin-4 receptor in complex with the Gs protein. Shows how the drug sits in the receptor's binding pocket, with a calcium ion helping to hold the ligand in place. Experimental structure (Cell Research 2021)."},{"id":"7AUE","description":"Cryo-EM structure (3.0 A) of the human MC4R-Gs signalling complex bound to setmelanotide, from a separate research group (Science 2021), which reports that calcium is needed for agonist, but not antagonist, efficacy at MC4R. Experimental structure."}]},"companies":["rhythm-pharmaceuticals"],"keyFacts":[{"label":"First FDA approval","value":"27 November 2020, for chronic weight management in people aged 6 and older with obesity due to POMC, PCSK1 or LEPR deficiency confirmed by genetic testing; the FDA called it the first FDA-approved treatment for these genetic conditions.","source":{"url":"https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-weight-management-people-certain-rare-genetic-conditions","title":"FDA approves first treatment for weight management for people with certain rare genetic conditions","publisher":"U.S. Food and Drug Administration","date":"2020-11-27","accessed":"2026-09-29"}},{"label":"Approval in acquired hypothalamic obesity","value":"19 March 2026 (FDA): to reduce excess body weight and maintain the reduction long term in adults and children aged 4 years and older with acquired hypothalamic obesity.","source":{"url":"https://www.sec.gov/Archives/edgar/data/1649904/000162828026019995/ex991hopdufapressrelease.htm","title":"Rhythm Pharmaceuticals Announces FDA Approval of IMCIVREE (setmelanotide) for Patients with Acquired Hypothalamic Obesity (Form 8-K, Exhibit 99.1)","publisher":"Rhythm Pharmaceuticals, Inc. (U.S. SEC filing)","date":"2026-03-19","accessed":"2026-09-29"}},{"label":"EU authorisation","value":"Authorised in the EU on 16 July 2021; the EMA page now lists acquired hypothalamic obesity (age 4+), Bardet-Biedl syndrome (age 2+) and biallelic POMC, PCSK1 or LEPR deficiency (age 2+). Marketing authorisation holder: Rhythm Pharmaceuticals Netherlands B.V.","source":{"url":"https://www.ema.europa.eu/en/medicines/human/EPAR/imcivree","title":"Imcivree (setmelanotide): EPAR summary page","publisher":"European Medicines Agency","date":"2026-05-27","accessed":"2026-09-29"}},{"label":"Original pivotal trials (FDA summary)","value":"In two one-year, open-label studies, 80% of patients with POMC or PCSK1 deficiency (10 enrolled) and 46% of patients with LEPR deficiency (11 enrolled) lost 10% or more of their body weight.","source":{"url":"https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-weight-management-people-certain-rare-genetic-conditions","title":"FDA approves first treatment for weight management for people with certain rare genetic conditions","publisher":"U.S. Food and Drug Administration","date":"2020-11-27","accessed":"2026-09-29"}},{"label":"TRANSCEND phase 3 (acquired hypothalamic obesity)","value":"120 participants aged 4 to 66, randomised 2:1. At 52 weeks BMI changed by -16.5% (95% CI -19.3 to -13.8) with setmelanotide versus +3.3% (95% CI -0.6 to 7.2) with placebo (P<0.001).","source":{"url":"https://doi.org/10.1056/NEJMoa2512275","title":"Setmelanotide for the Treatment of Acquired Hypothalamic Obesity","publisher":"New England Journal of Medicine","date":"2026-07-09","accessed":"2026-09-29"}},{"label":"Molecular weight and half-life","value":"Molecular mass 1117.3 Da (C49H68N18O9S2); elimination half-life about 11 hours.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9","title":"IMCIVREE (setmelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Rhythm Pharmaceuticals)","date":"2026-04-01","accessed":"2026-09-29"}}],"safety":[{"text":"The US label has no boxed warning. Warnings and precautions include depression and suicidal ideation; patients are to be monitored for new or worsening depression or suicidal thoughts, and discontinuation is considered if they occur.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9","title":"IMCIVREE (setmelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Rhythm Pharmaceuticals)","date":"2026-04-01","accessed":"2026-09-29"}},{"text":"Serious hypersensitivity reactions, including anaphylaxis, have been reported, with onset within minutes to hours of injection.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9","title":"IMCIVREE (setmelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Rhythm Pharmaceuticals)","date":"2026-04-01","accessed":"2026-09-29"}},{"text":"Skin hyperpigmentation occurred in the majority of treated patients and is reversible on stopping; darkening of existing nevi and new melanocytic nevi can occur, and the label calls for baseline and periodic full-body skin examinations.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9","title":"IMCIVREE (setmelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Rhythm Pharmaceuticals)","date":"2026-04-01","accessed":"2026-09-29"}},{"text":"Spontaneous penile erections and increased frequency of erections occurred in males in clinical trials (disturbance in sexual arousal warning); the label also notes sexual adverse reactions in females.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9","title":"IMCIVREE (setmelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Rhythm Pharmaceuticals)","date":"2026-04-01","accessed":"2026-09-29"}},{"text":"In acquired hypothalamic obesity the label adds warnings for acute adrenal insufficiency (in patients with secondary adrenal insufficiency) and for sodium imbalance (in patients who also have central diabetes insipidus), with monitoring of serum sodium.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9","title":"IMCIVREE (setmelanotide) injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Rhythm Pharmaceuticals)","date":"2026-04-01","accessed":"2026-09-29"}},{"text":"In TRANSCEND, adverse events were reported in 100% of setmelanotide participants and 90% of placebo participants, and serious adverse events in 28% and 8%. The most common with the drug were skin hyperpigmentation, nausea, vomiting and headache.","source":{"url":"https://doi.org/10.1056/NEJMoa2512275","title":"Setmelanotide for the Treatment of Acquired Hypothalamic Obesity","publisher":"New England Journal of Medicine","date":"2026-07-09","accessed":"2026-09-29"}}],"related":["bremelanotide","melanotan-ii","semaglutide"],"lastVerified":"2026-09-29"},{"slug":"survodutide","name":"Survodutide","url":"https://glp1base.com/molecules/survodutide","aliases":["BI 456906","BI-456906"],"brands":[],"class":"incretin-pipeline","classLabel":"In clinical trials","targets":["Glucagon receptor","GLP-1 receptor"],"summarySimple":"Survodutide is an experimental weekly injection that copies two natural hormones: GLP-1, made in the gut, and glucagon, made in the pancreas. It is being tested for obesity and for fatty liver disease. Large trials show weight loss and less liver fat, but it is not approved by any regulator we checked, and stomach side effects were common.","summaryExpert":"Survodutide (BI 456906) is a synthetic, once-weekly, subcutaneous dual agonist of the glucagon receptor (GCGR) and the GLP-1 receptor (GLP-1R). It is a 29-residue glucagon-based peptide amidated at the C-terminus, with a non-natural 1-aminocyclobutanecarboxylic acid residue at position 2 and a C18 fatty diacid attached, through a gamma-glutamate and a short glycine/serine linker, to the side chain of the lysine at position 24 (molecular formula C192H289N47O61, about 4,232 Da; PubChem). Acylation of this kind is the usual strategy for prolonging action in blood; a survodutide-specific terminal half-life was not verified from a primary source for this page. GLP-1R agonism reduces appetite and slows gastric emptying, while glucagon receptor agonism is thought to act directly on the liver and to add to energy balance effects; in humans, plasma glucagon and amino acids fall after dosing, consistent with engagement of both receptors. Survodutide is developed by Boehringer Ingelheim; Zealand Pharma is eligible for royalties and milestone payments under a licence agreement. It is investigational and is not approved by the FDA, EMA, MHRA, PMDA, NMPA, TGA or Health Canada; no marketing application was found in public sources as of 2026-09-29. The phase 3 SYNCHRONIZE programme in obesity has reported: SYNCHRONIZE-1 (NCT06066515, n=725, 76 weeks) showed mean body-weight change with the treatment-regimen estimand of -12.2% and -13.0% in the two survodutide groups versus -5.4% with placebo (published in NEJM), and -16.6% versus -3.2% with the efficacy estimand (company release). SYNCHRONIZE-MASLD (n=216, 48 weeks) met its liver-fat and weight co-primary endpoints. SYNCHRONIZE-2 (type 2 diabetes) is complete, and Zealand Pharma said in August 2026 that its results would be presented at the EASD annual meeting (28 September to 2 October 2026); the cardiovascular outcomes trial is listed as completed, with results expected later in 2026; and the LIVERAGE phase 3 trials in MASH are still recruiting. Gastrointestinal adverse events were the main safety finding.","evidence":{"level":"phase3","note":"Investigational, not approved anywhere that we could verify. Phase 3 obesity data are published: SYNCHRONIZE-1 (adults without diabetes, n=725, 76 weeks; NEJM 2026) and SYNCHRONIZE-MASLD (n=216, 48 weeks; Nature Medicine 2026). Earlier phase 2 trials in obesity (n=387, Lancet Diabetes & Endocrinology 2024) and in MASH with fibrosis (n=293, NEJM 2024) support the programme. Full results of SYNCHRONIZE-2 (type 2 diabetes; due at EASD 2026) and of the completed cardiovascular outcomes trial had not been published in the sources we reviewed, and phase 3 trials in MASH (LIVERAGE) are recruiting. The headline 16.6% weight loss comes from the trial's efficacy estimand (participants who stayed on treatment as planned); the primary published analysis, the treatment-regimen estimand, gave 12.2% and 13.0%.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/42253238/","title":"Survodutide Once Weekly for the Treatment of Adults with Obesity (SYNCHRONIZE-1)","publisher":"New England Journal of Medicine (PubMed)","date":"2026-06-07","accessed":"2026-09-29"},{"url":"https://www.globenewswire.com/news-release/2026/04/28/3282220/0/en/zealand-pharma-announces-boehringer-ingelheim-s-novel-glucagon-glp-1-dual-agonist-survodutide-achieved-significant-weight-loss-of-16-6-delivering-meaningful-metabolic-improvement-i.html","title":"Zealand Pharma announces Boehringer Ingelheim's novel glucagon/GLP-1 dual agonist survodutide achieved significant weight loss of 16.6% delivering meaningful metabolic improvement in people with obesity or overweight in Phase 3 trial","publisher":"Zealand Pharma (GlobeNewswire)","date":"2026-04-28","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/42252333/","title":"Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD","publisher":"Nature Medicine (PubMed)","date":"2026-06-07","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38330987/","title":"Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2024-02-05","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38847460/","title":"A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis","publisher":"New England Journal of Medicine (PubMed)","date":"2024-06-07","accessed":"2026-09-29"}],"label":"Phase 3 trials"},"route":"In clinical trials, survodutide has been given as a once-weekly injection under the skin (subcutaneous), with the amount increased gradually at the start of treatment. Pre-filled syringe and pen-type injector formulations have been compared in phase 1 bioequivalence studies. It has no approved route because it is not approved.","halfLife":null,"structure":{"pubchemCid":171378821,"pdb":[]},"companies":["boehringer-ingelheim","zealand-pharma"],"keyFacts":[{"label":"Regulatory status","value":"Investigational. Not approved by any regulator we could verify as of 2026-09-29, and no marketing application was found in public sources. The FDA granted Fast Track (May 2021) and Breakthrough Therapy (September 2024) designations, and the EMA accepted it into PRIME (November 2023).","source":{"url":"https://www.globenewswire.com/news-release/2026/04/28/3282220/0/en/zealand-pharma-announces-boehringer-ingelheim-s-novel-glucagon-glp-1-dual-agonist-survodutide-achieved-significant-weight-loss-of-16-6-delivering-meaningful-metabolic-improvement-i.html","title":"Zealand Pharma announces Boehringer Ingelheim's novel glucagon/GLP-1 dual agonist survodutide achieved significant weight loss of 16.6% delivering meaningful metabolic improvement in people with obesity or overweight in Phase 3 trial","publisher":"Zealand Pharma (GlobeNewswire)","date":"2026-04-28","accessed":"2026-09-29"}},{"label":"SYNCHRONIZE-1 primary result","value":"In 725 adults with obesity or overweight and no diabetes, mean body-weight change at week 76 (treatment-regimen estimand) was -12.2% and -13.0% in the two survodutide groups versus -5.4% with placebo; 72.6%, 71.9% and 46.3% lost at least 5% (P<0.001 for all comparisons with placebo).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42253238/","title":"Survodutide Once Weekly for the Treatment of Adults with Obesity (SYNCHRONIZE-1)","publisher":"New England Journal of Medicine (PubMed)","date":"2026-06-07","accessed":"2026-09-29"}},{"label":"Efficacy-estimand result","value":"Among people who stayed on treatment as planned, average weight loss was up to 16.6% versus 3.2% with placebo (p<0.0001), and 85.1% versus 38.8% lost at least 5%, as reported by the sponsors (efficacy estimand, not the primary published analysis).","source":{"url":"https://www.globenewswire.com/news-release/2026/04/28/3282220/0/en/zealand-pharma-announces-boehringer-ingelheim-s-novel-glucagon-glp-1-dual-agonist-survodutide-achieved-significant-weight-loss-of-16-6-delivering-meaningful-metabolic-improvement-i.html","title":"Zealand Pharma announces Boehringer Ingelheim's novel glucagon/GLP-1 dual agonist survodutide achieved significant weight loss of 16.6% delivering meaningful metabolic improvement in people with obesity or overweight in Phase 3 trial","publisher":"Zealand Pharma (GlobeNewswire)","date":"2026-04-28","accessed":"2026-09-29"}},{"label":"Phase 2 obesity trial","value":"At 46 weeks, mean weight change by planned treatment was -6.2%, -12.5%, -13.2% and -14.9% across four ascending dose groups versus -2.8% with placebo (n=387).","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/38330987/","title":"Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial","publisher":"The Lancet Diabetes & Endocrinology (PubMed)","date":"2024-02-05","accessed":"2026-09-29"}},{"label":"SYNCHRONIZE-MASLD","value":"In 216 adults with obesity and at-risk fatty liver disease (48 weeks), 84.2% versus 24.3% had a liver-fat fall of at least 30% and body weight fell 12.2% versus 1.0% (efficacy estimand); with the treatment-regimen estimand the figures were 68.5% versus 28.6% and 8.7% versus 1.4%.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42252333/","title":"Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD","publisher":"Nature Medicine (PubMed)","date":"2026-06-07","accessed":"2026-09-29"}},{"label":"Molecular weight","value":"About 4,232 Da; formula C192H289N47O61 (a 29-residue lipidated peptide).","source":{"url":"https://pubchem.ncbi.nlm.nih.gov/compound/171378821","title":"Compound Summary: CID 171378821 (survodutide)","publisher":"PubChem, National Library of Medicine","date":"2026","accessed":"2026-09-29"}}],"safety":[{"text":"Gastrointestinal adverse events were the main finding in SYNCHRONIZE-1: they occurred in 80.9% and 89.7% of the two survodutide groups versus 47.9% with placebo, and were typically mild to moderate. No deaths were reported.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/42253238/","title":"Survodutide Once Weekly for the Treatment of Adults with Obesity (SYNCHRONIZE-1)","publisher":"New England Journal of Medicine (PubMed)","date":"2026-06-07","accessed":"2026-09-29"}},{"text":"About 19% of survodutide-treated participants in SYNCHRONIZE-1 stopped treatment because of gastrointestinal events, versus 2.9% with placebo, per the sponsors' report of the full data.","source":{"url":"https://www.globenewswire.com/news-release/2026/06/07/3307740/0/en/zealand-pharma-announces-boehringer-ingelheim-s-survodutide-phase-iii-trial-in-people-living-with-obesity-showed-targeted-34-visceral-and-63-liver-fat-reduction-while-minimizing-le.html","title":"Zealand Pharma announces Boehringer Ingelheim's survodutide Phase III trial in people living with obesity showed targeted 34% visceral and 63% liver fat reduction, while minimizing lean mass loss in pre-specified analysis","publisher":"Zealand Pharma (GlobeNewswire)","date":"2026-06-07","accessed":"2026-09-29"}},{"text":"In the phase 2 MASH trial, adverse events more frequent with survodutide than placebo included nausea (66% vs 23%), diarrhoea (49% vs 23%) and vomiting (41% vs 4%); serious adverse events occurred in 8% versus 7%.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/38847460/","title":"A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis","publisher":"New England Journal of Medicine (PubMed)","date":"2024-06-07","accessed":"2026-09-29"}},{"text":"A published summary of SYNCHRONIZE-1 reports a mean heart-rate increase of 3.2 to 3.5 beats per minute and no confirmed cases of pancreatic cancer, thyroid cancer or acute pancreatitis; asymptomatic pancreatic enzyme elevations were slightly more common with survodutide.","source":{"url":"https://www.ajmc.com/view/survodutide-phase-3-data-signal-metabolic-gains-beyond-weight-loss","title":"Survodutide Phase 3 Data Signal Metabolic Gains Beyond Weight Loss","publisher":"AJMC","date":"2026-06-08","accessed":"2026-09-29"}},{"text":"Survodutide is not approved, so it has no label, and its long-term safety and cardiovascular safety have not been established. The cardiovascular outcomes trial and further phase 3 trials are still to report.","source":{"url":"https://www.globenewswire.com/news-release/2026/08/13/3344209/0/en/zealand-pharma-announces-financial-results-for-the-first-half-of-2026.html","title":"Zealand Pharma Announces Financial Results for the First Half of 2026","publisher":"Zealand Pharma (GlobeNewswire)","date":"2026-08-13","accessed":"2026-09-29"}}],"related":["retatrutide","mazdutide","tirzepatide","semaglutide"],"lastVerified":"2026-09-29"},{"slug":"tb-500","name":"TB-500 (thymosin beta-4 fragment)","url":"https://glp1base.com/molecules/tb-500","aliases":["TB-500","TB500","Ac-LKKTETQ","N-acetyl-LKKTETQ","Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH","Thymosin beta-4 fragment 17-23 (N-acetylated)"],"brands":[],"class":"peptide-trending","classLabel":"Trending peptide","targets":["G-actin (actin monomers): proposed through the LKKTET actin-binding motif of thymosin beta-4; not demonstrated for the N-acetylated peptide itself","No confirmed receptor or molecular target for TB-500 itself"],"summarySimple":"TB-500 is a tiny lab-made piece of a body protein called thymosin beta-4. It is not an approved medicine anywhere, and no studies in people have been found. A few animal and cell-dish studies looked at wound healing, mostly with the full protein or a slightly different piece. It is banned in sport.","summaryExpert":"TB-500 is a synthetic, N-terminally acetylated heptapeptide, Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln-OH (Ac-LKKTETQ), corresponding to residues 17-23 of the 43-residue human protein thymosin beta-4 (C38H68N10O14, 889.01 g/mol; the acetate salt is a separate bulk substance at 949.1 g/mol). Residues LKKTET form the central actin-binding motif of thymosin beta-4, which sequesters globular actin; whether the short acetylated fragment reproduces that buffering activity, or any other activity of the parent protein, has not been shown. FDA reviewers stress that TB-500 and thymosin beta-4 are not the same substance and that acetylation alters charge, hydrophobicity and binding, so results from the full protein or from the non-acetylated LKKTETQ peptide cannot be transferred directly. Evidence is preclinical. The non-acetylated LKKTETQ peptide promoted dermal repair in aged mice comparably to full-length thymosin beta-4 (Philp 2003, Wound Repair Regen), but in a 2024 cell-scratch assay TB-500 itself did not close fibroblast wounds, whereas its truncated metabolite Ac-LKKTE gave a small significant effect, raising the possibility that any activity depends on metabolic conversion (Rahaman 2024, J Chromatogr B). The only pharmacokinetic data are from horses given a single subcutaneous injection: plasma levels were sub-ng/mL, peaked 1-2 hours after injection and were unquantifiable after 6-10 hours; C-terminally truncated N-acetylated metabolites (Ac-LKKTET, Ac-LKKTE, Ac-LKKT, Ac-LKK, Ac-LK) form by sequential loss of residues; they were identified with equine liver in vitro, several were found in horse plasma and urine and in rat urine, and similar truncation occurred in human serum in vitro (Ho 2012; Rahaman 2024). Regulatory status: FDA's review states TB-500 is not a component of any FDA-approved drug, is not in the European or Japanese pharmacopoeias, and has no authorised products in the EU or in Canada, Australia, the UK and several other countries; FDA found no human studies of any kind. In its briefing for the July 2026 Pharmacy Compounding Advisory Committee, FDA staff concluded that the evaluation criteria weighed against adding TB-500 to the 503A Bulks List (wound-healing use: no human efficacy data and no in-vivo nonclinical wound-healing studies of TB-500; no toxicology data; injectable-peptide immunogenicity and aggregation concerns; poor characterisation). The committee nonetheless voted 8-6 with 1 abstention on 23 July 2026 to recommend it; the vote is non-binding, and FDA had not adopted it in any source verified as of 29 September 2026. The WADA Prohibited List names thymosin-beta-4 and its derivatives, e.g. TB-500, under S2.3 (banned at all times). Human clinical work exists only for full-length thymosin beta-4, for example a phase 2 topical trial in 73 patients with venous stasis ulcers and a small phase 2 trial of an eye-drop form in severe dry eye; none of it is evidence for TB-500.","evidence":{"level":"animal","note":"There are no published studies of TB-500 in people; FDA searched PubMed, Embase, ClinicalTrials.gov and adverse-event databases and found none. The best available evidence is animal and cell work: the non-acetylated LKKTETQ peptide (not TB-500) improved wound repair in aged mice, and full-length thymosin beta-4 (not TB-500) improved wound repair in rats. A 2024 cell study found that TB-500 itself did not close scratch wounds in fibroblasts while a metabolite did, and the only pharmacokinetic data are from horses (doping-control work). Human trials of the full-length protein exist but are not evidence for TB-500. Evidence level is therefore labelled animal, and it is indirect.","sources":[{"url":"https://www.fda.gov/media/193349/download","title":"FDA Evaluation of TB-500-Related Bulk Drug Substances (TB-500 (Free Base) and TB-500 acetate), briefing document for the Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05-15","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12581423/","title":"Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice","publisher":"Wound Repair and Regeneration (PubMed)","date":"2003","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38382158/","title":"Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro","publisher":"Journal of Chromatography B (PubMed)","date":"2024-03-01","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10469335/","title":"Thymosin beta4 accelerates wound healing","publisher":"Journal of Investigative Dermatology (PubMed)","date":"1999-09","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23084823/","title":"Doping control analysis of TB-500, a synthetic version of an active region of thymosin beta4, in equine urine and plasma by liquid chromatography-mass spectrometry","publisher":"Journal of Chromatography A (PubMed)","date":"2012-11-23","accessed":"2026-09-29"}],"label":"Animal studies only"},"route":"No approved route: TB-500 has no approved medical use. In the studies that exist, it was given by subcutaneous injection to horses (a doping-control study) and by intraperitoneal injection to rats (a metabolism study). Most wound-healing research used the full-length thymosin beta-4 protein, or the non-acetylated LKKTETQ peptide, mostly applied to skin wounds in mice and rats (one rat study also gave the full protein by intraperitoneal injection). FDA notes it was nominated for compounding as an injectable, but no human use has been studied.","halfLife":null,"structure":{"pubchemCid":62707662,"pdb":[{"id":"4PL7","description":"Crystal structure (2014) of a yeast actin fused to full-length human thymosin beta-4. It shows how the parent protein, which contains the LKKTETQ stretch that TB-500 copies, sits on an actin monomer. It is not a structure of TB-500 itself."}]},"companies":[],"keyFacts":[{"label":"What it is","value":"A synthetic heptapeptide, Ac-LKKTETQ: residues 17-23 of the 43-amino-acid protein thymosin beta-4 with an acetyl group on the first residue. Formula C38H68N10O14, molecular weight 889.01 g/mol. FDA reviewers state TB-500 and thymosin beta-4 are not the same substance.","source":{"url":"https://www.fda.gov/media/193349/download","title":"FDA Evaluation of TB-500-Related Bulk Drug Substances (TB-500 (Free Base) and TB-500 acetate), briefing document for the Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05-15","accessed":"2026-09-29"}},{"label":"Approval status","value":"Not a component of any FDA-approved drug and not recognised in the European or Japanese pharmacopoeias. FDA found no approved TB-500 products in Canada, Australia, the UK, Belgium, Ireland, France, Norway, Germany, Spain or Italy, and none authorised by the EMA.","source":{"url":"https://www.fda.gov/media/193349/download","title":"FDA Evaluation of TB-500-Related Bulk Drug Substances (TB-500 (Free Base) and TB-500 acetate), briefing document for the Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05-15","accessed":"2026-09-29"}},{"label":"Human studies","value":"FDA found no studies of TB-500 given to humans by any route, no human pharmacokinetic data and no published case reports.","source":{"url":"https://www.fda.gov/media/193349/download","title":"FDA Evaluation of TB-500-Related Bulk Drug Substances (TB-500 (Free Base) and TB-500 acetate), briefing document for the Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05-15","accessed":"2026-09-29"}},{"label":"FDA advisory committee vote (2026)","value":"FDA staff recommended against adding TB-500 to the 503A Bulks List for wound healing. On 23 July 2026 the Pharmacy Compounding Advisory Committee voted 8-6 with 1 abstention to recommend it. The vote is non-binding; FDA must still decide whether to accept it.","source":{"url":"https://www.ajmc.com/view/fda-panel-backs-6-peptides-for-compounding","title":"FDA panel backs 6 peptides for compounding","publisher":"The American Journal of Managed Care (AJMC)","date":"2026-07-31","accessed":"2026-09-29"}},{"label":"Metabolite finding (2024)","value":"In a fibroblast scratch assay TB-500 did not significantly close wounds versus control; its metabolite Ac-LKKTE did. The authors suggest earlier reports of TB-500 activity may reflect the metabolite.","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/38382158/","title":"Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro","publisher":"Journal of Chromatography B (PubMed)","date":"2024-03-01","accessed":"2026-09-29"}},{"label":"Anti-doping","value":"Thymosin-beta-4 and its derivatives, e.g. TB-500, were added as examples of prohibited growth factors under S2.3 of the WADA Prohibited List from 2018.","source":{"url":"https://www.usada.org/athlete-advisory/2018-prohibited-list-summary-of-major-changes/","title":"2018 Prohibited List: Summary of Major Changes","publisher":"U.S. Anti-Doping Agency (USADA)","date":"2017-10-02","accessed":"2026-09-29"}}],"safety":[{"text":"No safety data in humans exist: FDA identified no clinical studies or human exposure data for TB-500, so potential risks in humans are unknown.","source":{"url":"https://www.fda.gov/media/193349/download","title":"FDA Evaluation of TB-500-Related Bulk Drug Substances (TB-500 (Free Base) and TB-500 acetate), briefing document for the Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05-15","accessed":"2026-09-29"}},{"text":"No toxicology studies (acute, repeat-dose, genotoxicity, reproductive or carcinogenicity) of TB-500 were identified by FDA.","source":{"url":"https://www.fda.gov/media/193349/download","title":"FDA Evaluation of TB-500-Related Bulk Drug Substances (TB-500 (Free Base) and TB-500 acetate), briefing document for the Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05-15","accessed":"2026-09-29"}},{"text":"FDA is concerned that injected peptides such as TB-500 may pose a significant risk of immune reactions (immunogenicity), potentially amplified by aggregation and synthesis-related impurities.","source":{"url":"https://www.fda.gov/media/193349/download","title":"FDA Evaluation of TB-500-Related Bulk Drug Substances (TB-500 (Free Base) and TB-500 acetate), briefing document for the Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05-15","accessed":"2026-09-29"}},{"text":"Product quality is a documented concern: a representative certificate of analysis for TB-500 tested only appearance, identity and purity, not assay, impurities, bacterial endotoxin or aggregates, and FDA calls the substance not well characterised chemically, partly because names are used inconsistently.","source":{"url":"https://www.fda.gov/media/193349/download","title":"FDA Evaluation of TB-500-Related Bulk Drug Substances (TB-500 (Free Base) and TB-500 acetate), briefing document for the Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05-15","accessed":"2026-09-29"}},{"text":"FDA's adverse-event database search (through 26 March 2025) returned no TB-500 reports, and a search of FDA's food, dietary-supplement and cosmetic complaint system (1 January 2004 to 10 March 2025) found two reports about a blended TB-500 and BPC-157 product that did not include safety assessments; FDA notes that its adverse-event data have limitations and do not allow definitive conclusions about safety.","source":{"url":"https://www.fda.gov/media/193349/download","title":"FDA Evaluation of TB-500-Related Bulk Drug Substances (TB-500 (Free Base) and TB-500 acetate), briefing document for the Pharmacy Compounding Advisory Committee, July 23-24, 2026","publisher":"U.S. Food and Drug Administration","date":"2026-05-15","accessed":"2026-09-29"}},{"text":"The 2026 WADA Prohibited List names thymosin-beta-4 and its derivatives, e.g. TB-500, under S2.3 (growth factors and growth factor modulators); substances in class S2 are prohibited at all times, in and out of competition.","source":{"url":"https://www.wada-ama.org/en/prohibited-list","title":"The Prohibited List (2026)","publisher":"World Anti-Doping Agency (WADA)","date":"2026","accessed":"2026-09-29"}}],"related":["bpc-157","kpv","ghk-cu"],"lastVerified":"2026-09-29"},{"slug":"tesamorelin","name":"Tesamorelin","url":"https://glp1base.com/molecules/tesamorelin","aliases":["TH9507","GHRH(1-44) with N-terminal hexenoyl group","N-trans-3-hexenoyl-GHRH(1-44) amide","Growth hormone-releasing factor analogue"],"brands":[{"name":"Egrifta (Egrifta SV, Egrifta WR)","company":"theratechnologies","indication":"Reduction of excess abdominal fat in HIV-infected adults with lipodystrophy (US)"}],"class":"peptide-approved","classLabel":"Approved peptide medicine","targets":["Growth hormone-releasing hormone (GHRH) receptor on pituitary somatotroph cells"],"summarySimple":"Tesamorelin is a lab-made copy of a natural brain hormone that tells the pituitary gland to release growth hormone. It is approved in the US for one narrow use: reducing extra belly fat in adults with HIV who have a fat-distribution problem called lipodystrophy. It is not approved for general weight loss.","summaryExpert":"Tesamorelin is a 44-residue synthetic analogue of human growth hormone-releasing hormone, GHRH(1-44) amide, carrying a trans-3-hexenoyl group on the N-terminal tyrosine (C221H366N72O67S; 5135.9 Da as free base). The 44 residues match the endogenous sequence; the hexenoyl group is the engineered modification. It binds and activates the GHRH receptor (a class B G protein-coupled receptor) on pituitary somatotrophs with potency similar to endogenous GHRH, stimulating pulsatile growth hormone (GH) release and raising IGF-1 and IGFBP-3, with no clinically significant changes in TSH, LH, ACTH or prolactin in trials. After subcutaneous injection, absolute bioavailability is under 4%, median Tmax is 0.15 h and the elimination half-life is about 11 minutes for the current Egrifta WR formulation (26 to 38 minutes reported for the original formulation). The FDA approved Egrifta on 10 November 2010 for reducing excess abdominal fat in HIV-infected patients with lipodystrophy; Egrifta SV and, in March 2025, Egrifta WR are newer formulations. In two pooled phase 3 trials (806 patients, 26 weeks) visceral adipose tissue fell by a treatment effect of 15.4%, with triglyceride improvement and an IGF-1 rise. The label warns of neoplasm risk, IGF-1 elevation, fluid retention, glucose intolerance and hypersensitivity. The EU application was withdrawn in 2012; Health Canada approved it in 2014, but its Drug Product Database has listed the marketed Egrifta product as cancelled since September 2022. Approval status at PMDA, NMPA, TGA and MHRA was not verified. Other uses (for example fatty liver in HIV) are unapproved and investigational.","evidence":{"level":"approved","note":"Approved by the US FDA (2010) on the basis of two randomised, double-blind, placebo-controlled 26-week phase 3 trials in HIV-infected adults with excess abdominal fat, each followed by a 26-week safety extension (806 patients pooled). Evidence is specific to HIV-associated abdominal fat; long-term cardiovascular outcomes have not been shown. Small randomised trials in HIV-associated fatty liver disease exist but are exploratory, and that use is unapproved.","sources":[{"url":"https://pubmed.ncbi.nlm.nih.gov/18057338/","title":"Metabolic effects of a growth hormone-releasing factor in patients with HIV (Falutz et al.)","publisher":"N Engl J Med (via PubMed)","date":"2007-12-06","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20554713/","title":"Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data","publisher":"J Clin Endocrinol Metab (via PubMed)","date":"2010-09","accessed":"2026-09-29"},{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75","title":"EGRIFTA WR (tesamorelin) for injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Theratechnologies)","date":"2025-03","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25038357/","title":"Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial","publisher":"JAMA (via PubMed)","date":"2014-07","accessed":"2026-09-29"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31611038/","title":"Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial","publisher":"Lancet HIV (via PubMed)","date":"2019-12","accessed":"2026-09-29"}],"label":"Approved"},"route":"Subcutaneous injection once daily, into the abdomen, in the approved HIV-lipodystrophy use (US label). It is a prescription product for use under medical supervision; it is not taken by mouth.","halfLife":{"value":"About 11 minutes for Egrifta WR in healthy subjects (26 minutes in healthy subjects and 38 minutes in HIV-infected patients for the original 2010 formulation)","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75","title":"EGRIFTA WR (tesamorelin) for injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Theratechnologies)","date":"2025-03","accessed":"2026-09-29"}},"structure":{"pubchemCid":16137828,"pdb":[{"id":"7CZ5","description":"Cryo-EM structure (2.6 A resolution) of the human GHRH receptor bound to Gs protein and human GHRH(1-44). Tesamorelin has the same 44-residue sequence as GHRH plus an N-terminal hexenoyl group, so this shows how the natural hormone that tesamorelin copies sits in its receptor. It is not tesamorelin itself."},{"id":"2XDG","description":"Crystal structure (1.95 A resolution) of the extracellular domain of the human GHRH receptor. It contains the receptor domain only, not tesamorelin or GHRH."}]},"companies":["theratechnologies"],"keyFacts":[{"label":"US approval","value":"FDA approved Egrifta (tesamorelin for injection) on 10 November 2010 for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy (NDA 022505).","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/022505s000ltr.pdf","title":"NDA 022505 approval letter, Egrifta (tesamorelin for injection)","publisher":"U.S. Food and Drug Administration, Drugs@FDA","date":"2010-11-10","accessed":"2026-09-29"}},{"label":"Egrifta WR","value":"The FDA approved Egrifta WR, a newer once-daily formulation, on 25 March 2025 for the same indication in adults with HIV and lipodystrophy.","source":{"url":"https://www.sec.gov/Archives/edgar/data/1512717/000119312525063760/d944896dex991.htm","title":"Theratechnologies Receives FDA Approval for EGRIFTA WR (Tesamorelin F8) to Treat Excess Visceral Abdominal Fat in Adults with HIV and Lipodystrophy","publisher":"Theratechnologies Inc. (Form 6-K, Exhibit 99.1, SEC EDGAR)","date":"2025-03-25","accessed":"2026-09-29"}},{"label":"Original US label","value":"Initial U.S. approval 2010; label revised 11/2010; not indicated for weight loss management (weight neutral effect)","source":{"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022505s000lbl.pdf","title":"EGRIFTA (tesamorelin for injection), original prescribing information","publisher":"U.S. Food and Drug Administration, Drugs@FDA","date":"2010-11","accessed":"2026-09-29"}},{"label":"Molecular weight","value":"5135.9 Da (free base equivalent); formula C221H366N72O67S; 44 amino acids plus an N-terminal hexenoyl group","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75","title":"EGRIFTA WR (tesamorelin) for injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Theratechnologies)","date":"2025-03","accessed":"2026-09-29"}},{"label":"Phase 3 result (NEJM 2007)","value":"In 412 patients over 26 weeks, visceral adipose tissue fell 15.2% with tesamorelin and rose 5.0% with placebo; IGF-1 rose 81.0% versus a 5.0% fall","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/18057338/","title":"Metabolic effects of a growth hormone-releasing factor in patients with HIV (Falutz et al.)","publisher":"N Engl J Med (via PubMed)","date":"2007-12-06","accessed":"2026-09-29"}},{"label":"Pooled phase 3 (806 patients)","value":"Treatment effect on visceral fat at week 26 was -15.4% (P<0.001); abdominal subcutaneous fat did not change significantly (-0.6%)","source":{"url":"https://pubmed.ncbi.nlm.nih.gov/20554713/","title":"Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data","publisher":"J Clin Endocrinol Metab (via PubMed)","date":"2010-09","accessed":"2026-09-29"}},{"label":"Half-life","value":"About 11 minutes for Egrifta WR (single dose, healthy subjects); bioavailability under 4%","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75","title":"EGRIFTA WR (tesamorelin) for injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Theratechnologies)","date":"2025-03","accessed":"2026-09-29"}},{"label":"EU","value":"The EU application by Ferrer was withdrawn in June 2012 after the CHMP considered the data did not allow a positive benefit-risk conclusion","source":{"url":"https://www.ema.europa.eu/en/news/ferrer-internacional-sa-withdraws-its-marketing-authorisation-application-egrifta-tesamorelin","title":"Ferrer Internacional, S.A. withdraws its marketing authorisation application for Egrifta (tesamorelin)","publisher":"European Medicines Agency","date":"2012-06-26","accessed":"2026-09-29"}},{"label":"Canada","value":"Theratechnologies announced on 30 April 2014 that Health Canada had issued a notice of compliance for Egrifta in treatment-experienced HIV-infected adults with excess visceral fat","source":{"url":"https://www.biospace.com/health-canada-approves-egrifta-and-0153-tesamorelin-for-injection-and-theratechnologies-inc-regains-canadian-commercialization-rights-to-egrifta-and-015","title":"Health Canada approves EGRIFTA (tesamorelin for injection) and Theratechnologies regains Canadian commercialization rights","publisher":"Theratechnologies Inc. (press release via BioSpace)","date":"2014-04-30","accessed":"2026-09-29"}},{"label":"Canada (current listing)","value":"Health Canada's Drug Product Database lists the marketed Egrifta product (DIN 02438712, first marketed June 2015) as cancelled post-market since 30 September 2022","source":{"url":"https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=92311","title":"Drug Product Database: EGRIFTA (DIN 02438712)","publisher":"Health Canada","date":"2022-09-30","accessed":"2026-09-29"}}],"safety":[{"text":"Contraindicated in disruption of the hypothalamic-pituitary axis, active malignancy, known hypersensitivity and pregnancy. Because it induces release of growth hormone, a known growth factor, it must not be used with active cancer; the label also asks for careful consideration before starting, given the higher background cancer risk in people with HIV.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75","title":"EGRIFTA WR (tesamorelin) for injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Theratechnologies)","date":"2025-03","accessed":"2026-09-29"}},{"text":"It raises IGF-1. In the trials 47% of treated patients had IGF-1 above 2 SDS and 36% above 3 SDS at 26 weeks; the label calls for IGF-1 monitoring and says the effects of prolonged elevation are unknown.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75","title":"EGRIFTA WR (tesamorelin) for injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Theratechnologies)","date":"2025-03","accessed":"2026-09-29"}},{"text":"Most common adverse reactions (over 5%) were arthralgia, injection site erythema, injection site pruritus, pain in extremity, peripheral edema and myalgia. Fluid retention, including carpal tunnel syndrome, can occur.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75","title":"EGRIFTA WR (tesamorelin) for injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Theratechnologies)","date":"2025-03","accessed":"2026-09-29"}},{"text":"Glucose intolerance and diabetes can develop: HbA1c of 6.5% or more occurred in 5% of tesamorelin patients versus 1% on placebo up to week 26 (hazard ratio 3.3).","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75","title":"EGRIFTA WR (tesamorelin) for injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Theratechnologies)","date":"2025-03","accessed":"2026-09-29"}},{"text":"Hypersensitivity reactions occurred in clinical trials, and anti-tesamorelin antibodies were found in 50% of patients treated for 26 weeks with the original formulation. The label also notes increased mortality in acute critical illness.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75","title":"EGRIFTA WR (tesamorelin) for injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Theratechnologies)","date":"2025-03","accessed":"2026-09-29"}},{"text":"Limitations of use on the label: long-term cardiovascular safety has not been established, it is not indicated for weight loss, and there are no data showing improved adherence to antiretroviral therapy.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75","title":"EGRIFTA WR (tesamorelin) for injection, prescribing information (DailyMed label)","publisher":"U.S. National Library of Medicine, DailyMed (label: Theratechnologies)","date":"2025-03","accessed":"2026-09-29"}}],"related":["sermorelin","cjc-1295","ipamorelin"],"lastVerified":"2026-09-29"},{"slug":"tirzepatide","name":"Tirzepatide","url":"https://glp1base.com/molecules/tirzepatide","aliases":["LY3298176"],"brands":[{"name":"Mounjaro","company":"eli-lilly","indication":"Type 2 diabetes (adults and children 10 and older); reducing major cardiovascular events in adults with type 2 diabetes at high risk (US label)"},{"name":"Zepbound","company":"eli-lilly","indication":"Chronic weight management in adults with obesity, or overweight with a weight-related condition; moderate-to-severe obstructive sleep apnea in adults with obesity (US label)"}],"class":"glp1-approved","classLabel":"Approved GLP-1 medicine","targets":["GIP receptor","GLP-1 receptor"],"summarySimple":"Tirzepatide is a small protein-like drug (a peptide, 39 building blocks long) that copies two gut hormones, GIP and GLP-1. Together they help the body control blood sugar and appetite. A fatty side chain lets it hitch a ride on a blood protein, so half of it is still there after about five days, and it is given once a week. It is approved for type 2 diabetes and weight management, and in the US for sleep apnea.","summaryExpert":"Tirzepatide is a 39-residue synthetic peptide, based on the GIP sequence, that is an agonist at both the GIP receptor and the GLP-1 receptor. It carries aminoisobutyric acid (Aib) at positions 2 and 13 and a C-terminal amide, and Lys20 is acylated through a linker with a C20 fatty diacid (1,20-eicosanedioic acid) that enables albumin binding (about 99% bound). Molecular weight is 4813.53 Da (C225H348N48O68). After subcutaneous injection, absolute bioavailability is about 80% and time to maximum concentration is 8 to 72 hours. Elimination half-life is about 5 days in type 2 diabetes and 5 to 6 days in obesity, supporting once-weekly administration. Metabolism is by proteolytic cleavage of the backbone, beta-oxidation of the diacid and amide hydrolysis; intact drug is not found in urine or faeces. In vitro, tirzepatide behaves like native GIP at the GIP receptor and is biased at the GLP-1 receptor toward cAMP over beta-arrestin recruitment, and modelled receptor occupancy is higher at the GIP receptor than at the GLP-1 receptor. The FDA approved it (as Mounjaro) for type 2 diabetes on 13 May 2022 and (as Zepbound) for chronic weight management on 8 November 2023, and added obstructive sleep apnea on 20 December 2024. It is authorised in the EU for type 2 diabetes and weight management. Key trials: SURPASS-2 (greater HbA1c reduction than semaglutide at 40 weeks), SURMOUNT-1 (mean weight change of up to -20.9% at 72 weeks versus -3.1% with placebo), SURMOUNT-5 (-20.2% versus -13.7% with semaglutide), SURMOUNT-OSA, SUMMIT (HFpEF with obesity) and SURPASS-CVOT (non-inferior to dulaglutide for major cardiovascular events).","evidence":{"level":"approved","note":"Approved by the US FDA and the European Medicines Agency after large randomised phase 3 programmes: SURPASS (type 2 diabetes), SURMOUNT (obesity and sleep apnea), SUMMIT (heart failure with preserved ejection fraction and obesity) and SURPASS-CVOT (cardiovascular outcomes versus dulaglutide). The two head-to-head trials against semaglutide (SURPASS-2 and SURMOUNT-5) were open-label. The manufacturer funded the pivotal trials.","sources":[{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2206038","title":"Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)","publisher":"New England Journal of Medicine","date":"2022-07-21","accessed":"2026-09-29"},{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2107519","title":"Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2)","publisher":"New England Journal of Medicine","date":"2021-08-05","accessed":"2026-09-29"},{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2416394","title":"Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5)","publisher":"New England Journal of Medicine","date":"2025-07-03","accessed":"2026-09-29"},{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2404881","title":"Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA)","publisher":"New England Journal of Medicine","date":"2024-10-03","accessed":"2026-09-29"},{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2410027","title":"Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity (SUMMIT)","publisher":"New England Journal of Medicine","date":"2025-01-30","accessed":"2026-09-29"},{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2505928","title":"Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes (SURPASS-CVOT)","publisher":"New England Journal of Medicine","date":"2025-12-18","accessed":"2026-09-29"},{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0","title":"MOUNJARO (tirzepatide) injection, prescribing information","publisher":"U.S. National Library of Medicine (DailyMed), FDA-approved label","date":"2026-09","accessed":"2026-09-29"},{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b","title":"ZEPBOUND (tirzepatide) injection, prescribing information","publisher":"U.S. National Library of Medicine (DailyMed), FDA-approved label","date":"2026-09","accessed":"2026-09-29"}],"label":"Approved"},"route":"Subcutaneous injection, given once a week, supplied as prefilled pens or vials","halfLife":{"value":"About 5 days (5 to 6 days in adults with obesity)","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b","title":"ZEPBOUND (tirzepatide) injection, prescribing information","publisher":"U.S. National Library of Medicine (DailyMed), FDA-approved label","date":"2026-09","accessed":"2026-09-29"}},"structure":{"pubchemCid":156588324,"pdb":[{"id":"7RBT","description":"Cryo-EM structure (3.08 Å) of the human GIP receptor bound to tirzepatide, in complex with Gs protein (Sun et al., PNAS 2022)."},{"id":"7VAB","description":"Cryo-EM structure (3.2 Å) of the human GIP receptor and Gs complex bound to a non-acylated form of tirzepatide, that is, the peptide without its fatty diacid (Nature Communications 2022)."},{"id":"7VBI","description":"Cryo-EM structure (3.0 Å) of the human GLP-1 receptor and Gs complex bound to the same non-acylated tirzepatide (Nature Communications 2022)."},{"id":"7FIM","description":"Cryo-EM structure of the tirzepatide (LY3298176)-bound human GLP-1R-Gs complex"},{"id":"7FIY","description":"Cryo-EM structure of the tirzepatide-bound human GIPR-Gs complex"}]},"companies":["eli-lilly"],"keyFacts":[{"label":"FDA approval for type 2 diabetes","value":"Approved on 13 May 2022 as Mounjaro, to improve blood sugar control in adults with type 2 diabetes as an addition to diet and exercise.","source":{"url":"https://www.fda.gov/drugs/drug-trials-snapshots/drug-trials-snapshots-mounjaro","title":"Drug Trials Snapshots: MOUNJARO","publisher":"U.S. Food and Drug Administration","date":"2023-06-13","accessed":"2026-09-29"}},{"label":"FDA approval for weight management","value":"Approved on 8 November 2023 as Zepbound for chronic weight management in adults with obesity, or overweight with a weight-related condition.","source":{"url":"https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management","title":"FDA Approves New Medication for Chronic Weight Management","publisher":"U.S. Food and Drug Administration","date":"2023-11-08","accessed":"2026-09-29"}},{"label":"FDA approval for sleep apnea","value":"Zepbound approved on 20 December 2024 for moderate-to-severe obstructive sleep apnea in adults with obesity.","source":{"url":"https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea","title":"FDA Approves First Medication for Obstructive Sleep Apnea","publisher":"U.S. Food and Drug Administration","date":"2024-12-20","accessed":"2026-09-29"}},{"label":"EU authorisation","value":"Marketing authorisation for Mounjaro granted on 15 September 2022; the EU indications cover type 2 diabetes (adults and children 10 and older) and weight management in adults. Sleep apnea is not a separate EU indication.","source":{"url":"https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro","title":"Mounjaro (tirzepatide): European public assessment report","publisher":"European Medicines Agency","date":"2022-09-15","accessed":"2026-09-29"}},{"label":"SURMOUNT-1 weight change at 72 weeks","value":"-20.9% at the highest of three maintenance doses versus -3.1% with placebo (2,539 adults with obesity, or overweight with a weight-related condition, and without diabetes).","source":{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2206038","title":"Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)","publisher":"New England Journal of Medicine","date":"2022-07-21","accessed":"2026-09-29"}},{"label":"SURMOUNT-5 versus semaglutide","value":"-20.2% with tirzepatide versus -13.7% with semaglutide at 72 weeks (751 adults, open-label).","source":{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2416394","title":"Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5)","publisher":"New England Journal of Medicine","date":"2025-07-03","accessed":"2026-09-29"}}],"safety":[{"text":"Boxed warning: in rats, tirzepatide caused thyroid C-cell tumours at clinically relevant exposures. It is unknown whether it causes these tumours, including medullary thyroid carcinoma, in humans. It is contraindicated in people with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b","title":"ZEPBOUND (tirzepatide) injection, prescribing information","publisher":"U.S. National Library of Medicine (DailyMed), FDA-approved label","date":"2026-09","accessed":"2026-09-29"}},{"text":"In SURPASS-2, the most common adverse events with tirzepatide were gastrointestinal and mostly mild to moderate: nausea in 17 to 22%, diarrhoea in 13 to 16% and vomiting in 6 to 10% of the three tirzepatide groups. Serious adverse events were reported in 5 to 7% of tirzepatide patients and 3% of semaglutide patients.","source":{"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2107519","title":"Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2)","publisher":"New England Journal of Medicine","date":"2021-08-05","accessed":"2026-09-29"}},{"text":"US labels list nausea, diarrhoea, vomiting, constipation, abdominal pain and dyspepsia among the most common adverse reactions (5% or more of patients), and warn of serious gastrointestinal reactions (not recommended in severe gastroparesis), acute kidney injury from dehydration, acute gallbladder disease and acute pancreatitis.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b","title":"ZEPBOUND (tirzepatide) injection, prescribing information","publisher":"U.S. National Library of Medicine (DailyMed), FDA-approved label","date":"2026-09","accessed":"2026-09-29"}},{"text":"The label states that the risk of hypoglycaemia, including severe hypoglycaemia, is increased when tirzepatide is used with insulin or an insulin secretagogue such as a sulfonylurea.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0","title":"MOUNJARO (tirzepatide) injection, prescribing information","publisher":"U.S. National Library of Medicine (DailyMed), FDA-approved label","date":"2026-09","accessed":"2026-09-29"}},{"text":"Because it delays gastric emptying, tirzepatide can affect the absorption of oral medicines, and there are rare postmarketing reports of pulmonary aspiration in people taking GLP-1 receptor agonists who had elective procedures under general anaesthesia or deep sedation.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b","title":"ZEPBOUND (tirzepatide) injection, prescribing information","publisher":"U.S. National Library of Medicine (DailyMed), FDA-approved label","date":"2026-09","accessed":"2026-09-29"}},{"text":"Other label warnings include serious hypersensitivity reactions (anaphylaxis, angioedema) reported after marketing, monitoring for diabetic retinopathy complications in people with type 2 diabetes and a history of retinopathy, and possible fetal harm in pregnancy.","source":{"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b","title":"ZEPBOUND (tirzepatide) injection, prescribing information","publisher":"U.S. National Library of Medicine (DailyMed), FDA-approved label","date":"2026-09","accessed":"2026-09-29"}}],"related":["semaglutide","dulaglutide","retatrutide","maridebart-cafraglutide"],"lastVerified":"2026-09-29"}]}