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In clinical trials

Maridebart cafraglutide (MariTide)

Also called MariTide, AMG 133, AMG133, maridebart.

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.

Maridebart cafraglutide (MariTide) is not an approved medicine for these uses in most countries. This page explains the science and the law; it does not give dosing, sourcing or usage advice.

How strong is the evidence?

AnecdoteAnimalsHuman trialsApproved
Phase 2. Mid-size trials testing if it works.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.

Last verified 2026-09-29 · how we verify

43. G · Glycine7. T · Threonine25. W · Tryptophan32. G · Glycine14. L · Leucine36. S · Serine18. A · Alanine3. E · Glutamate21. E · Glutamate39. G · Glycine47. K · Lysine29. G · Glycine11. S · Serine28. K · Lysine10. Y · Tyrosine46. S · Serine40. G · Glycine4. G · Glycine22. F · Phenylalanine17. Q · Glutamine35. G · Glycine15. E · Glutamate33. G · Glycine6. F · Phenylalanine24. A · Alanine42. G · Glycine8. S · Serine44. G · Glycine26. L · Leucine13. Y · Tyrosine31. G · Glycine37. G · Glycine1. H · Histidine19. A · Alanine2. X · Modified or non-standard residue20. K · Lysine38. G · Glycine30. G · Glycine12. S · Serine9. D · Aspartate27. V · Valine45. G · Glycine41. S · Serine5. T · Threonine23. I · Isoleucine34. G · Glycine16. E · GlutamateNC

Schematic

  • Positive charge
  • Modified or non-standard (X)
  • Negative charge
  • Glycine or proline
  • Water-loving
  • Water-avoiding

Schematic from the amino-acid sequence — not an experimental structure

47 amino acids, one bead each, coloured by type, N-terminus to C-terminus. The helix shape is illustrative; it is not the real 3D shape of Maridebart cafraglutide (MariTide).

Acts on
GIP receptor (antagonist antibody), GLP-1 receptor (agonist peptides)
Taken as
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.
Half-life
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)[src]
Molecule format
Fully human anti-GIPR IgG1 antibody linked to two GLP-1 analogue peptides; average molecular weight 153,514 Da[src]
Half-life in people
About 21 days (mean, first-in-human phase 1 study)[src]
Phase 2 obesity result (52 weeks)
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)[src]

Inside the body

What Maridebart cafraglutide (MariTide) does, step by step

Watch the 3D journey →
  1. 01Skin

    Given as a slow-release injection under the skin

    In the trials, the medicine was injected under the skin about once a month. It then moves slowly into the blood.

    For experts

    Phase 1 and phase 2 studies used subcutaneous administration every 4 weeks; one phase 2 arm used every 8 weeks without dose escalation. Amgen states that the long-acting design supports starting with monthly dosing and staying on treatment with as few as 4 or 6 doses per year, and its phase 3 switch and extension studies test every-8-week and quarterly schedules. This is a development plan, not an approved regimen.[src][src]

  2. 02Bloodstream

    An antibody carrier keeps it in the blood for weeks

    Small peptide medicines are usually cleared from the blood within hours or days. Here the peptides are attached to an antibody, which the body clears very slowly. The half-life (the time for half of it to leave the blood) is about 21 days.

    For experts

    Conjugation of two GLP-1 analogue peptides to an IgG1 gave a mean half-life of about 21 days in the phase 1 study (about 21 to 24 days for total drug, 14 to 16 days for intact conjugate in single-dose cohorts), compared with about 1 week for semaglutide. In mice and monkeys, assays distinguished 'intact' conjugate (at least one peptide still attached) from 'total' antibody; intact conjugate cleared faster, indicating that peptide loss from the antibody contributes to clearance of active drug (animal data). The J Med Chem discovery paper reports that conjugating GLP-1 peptides to anti-GIPR antibodies gave markedly prolonged systemic exposure of the structurally intact GLP-1 peptide.[src][src][src]

  3. 03Elsewhere

    The antibody part blocks GIP receptors

    GIP is a gut hormone. The antibody sticks to the GIP receptor and stops GIP from switching it on. Why this helps with weight is still being worked out, and some scientists are debating it.

    For experts

    The antibody is a GIPR antagonist: in cell cAMP assays it inhibited GIP signalling through human GIPR (IC50 42.4 nM) and cynomolgus GIPR (26.5 nM), but was more than 20-fold weaker at rat GIPR and did not fully block mouse GIPR, so a mouse-specific surrogate antibody conjugate was used for mouse studies. The stated rationale is human genome-wide association data linking the GIPR locus (and lower GIPR function) to body weight, protection of GIPR knockout mice from diet-induced obesity, and earlier Amgen work in which GIPR antagonism combined with GLP-1R agonism reduced body weight synergistically in obese mice and monkeys (animal data). The phase 1 authors state it is unclear how to reconcile this with the added weight loss seen with GIPR/GLP-1R dual agonists, and that the precise mechanism in humans is not known.[src][src]

  4. 04Brain

    The peptides switch on GLP-1 receptors, which is thought to turn down appetite

    The two small peptides copy GLP-1, a gut hormone that helps signal fullness. Other GLP-1 medicines turn down appetite, partly through brain areas that control hunger. MariTide is a very large molecule that probably cannot cross into most of the brain, so it may act on nerve areas that sit outside the brain's barrier. That idea has only been looked at in animals. For MariTide, the proven part is the weight loss in trials.

    For experts

    The conjugate is a full agonist of human GLP-1R in cAMP assays (EC50 24.4 pM). For the approved GLP-1R agonist semaglutide, the label states that GLP-1 receptors are present in brain areas involved in appetite regulation and that, in animals, semaglutide reached and activated neurons in those regions; rodent work shows it acts via circumventricular organs without crossing the blood-brain barrier. In adults with obesity, semaglutide reduced appetite ratings and ad libitum energy intake. For maridebart cafraglutide, the phase 1 authors note that as a large antibody conjugate it likely does not cross the blood-brain barrier, and that reduced food intake in obese mice (surrogate) and monkeys may reflect peripheral effects or receptors outside the barrier such as in the area postrema (animal data). No appetite or energy-intake study of MariTide in humans was found.[src][src][src][src]

  5. 05Pancreas

    Blood sugar falls in people with type 2 diabetes

    GLP-1 receptors on pancreas cells help the body release insulin when blood sugar is high. In the trial in people with diabetes, average blood sugar fell clearly.

    For experts

    In the obesity-diabetes cohort of the phase 2 trial, mean HbA1c fell by 1.2 to 1.6 percentage points in maridebart cafraglutide groups versus 0.1 with placebo at week 52 (treatment-policy estimand). In phase 1 participants with obesity, fasting glucose fell dose-dependently. The split between weight-dependent and direct pancreatic effects was not resolved in these trials.[src][src]

  6. 06Stomach

    Food may leave the stomach more slowly

    GLP-1 medicines can slow how fast the stomach empties. Amgen has finished a study measuring this for MariTide, but no results had been published as of September 2026.

    For experts

    The semaglutide label states that semaglutide delays gastric emptying; however, in a 20-week study of semaglutide in adults with obesity there was no evidence of delayed gastric emptying at week 20 by paracetamol absorption, so the size of this effect with long-term dosing is uncertain. A dedicated phase 1 gastric emptying study of AMG 133 (NCT07429032, paracetamol absorption endpoints) is listed as completed, but no results were found as of 2026-09-29, so this step is inferred from class pharmacology and unconfirmed for this molecule. Nausea and vomiting were its most common adverse events.[src][src][src][src]

  7. 07Fat tissue

    Body weight comes down over months

    In a one-year trial, adults with obesity who took MariTide lost on average about 12 to 16 percent of their body weight, compared with about 2.5 percent on placebo. People who also had type 2 diabetes lost about 8 to 12 percent, compared with about 2 percent on placebo. Weight had not levelled off at one year, and results from longer trials are not known yet.

    For experts

    Phase 2 obesity cohort (n=465): mean weight change -12.3% to -16.2% at week 52 (treatment-policy estimand) versus -2.5% placebo; Amgen reports up to about 20% on the efficacy estimand versus 2.6% placebo, with weight loss not having plateaued by 52 weeks. Obesity-diabetes cohort (n=127): -8.4% to -12.3% versus -1.7% placebo (treatment-policy estimand). In phase 1 multiple-dose cohorts, weight loss was maintained for up to 150 days after the last dose. A mouse surrogate conjugate reduced body weight in obese mice, and AMG 133 reduced body weight in obese cynomolgus monkeys (animal data). Durability beyond 52 weeks is being studied in phase 3.[src][src][src]

For experts

The detail

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: 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.[src][src][src][src][src]

Known safety signals

  • 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.[src]
  • 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.[src]
  • 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.[src]
  • 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.[src]

Around the world

Is Maridebart cafraglutide (MariTide) legal where you live?

CountryStatusWhat it meansVerified
AustraliaNot approvedInvestigational only. No maridebart cafraglutide product is on the ARTG and no application appears on the TGA's evaluation list.Details →source2026-09-29
BrazilNot approvedMaridebart cafraglutide has no Brazilian registration and is not on the marketDetails →source2026-09-29
CanadaNot approvedMaridebart cafraglutide (MariTide) is an investigational drug with no Health Canada authorisationDetails →source2026-09-29
ChinaNot approvedNot approved in China; Amgen has trial-stage filings and Chinese sites in its outcomes trial.Details →source2026-09-29
European UnionNot approvedInvestigational; no EU marketing authorisation and no application under evaluationDetails →source2026-09-29
IndiaNot approvedNot approved in India: no CDSCO marketing permission or Indian trial record found for maridebart cafraglutideDetails →source2026-09-29
JapanNot approvedNo marketing approval in Japan; the investigational antibody-peptide conjugate maridebart cafraglutide does not appear in PMDA's approved-drug lists to September 2026Details →source2026-09-29
MexicoNot approvedNot registered in Mexico; MariTide is an investigational Amgen medicineDetails →source2026-09-29
New ZealandNot approvedMaridebart cafraglutide (MariTide) is investigational with no Medsafe consent in New ZealandDetails →source2026-09-29
United Arab EmiratesNot approvedNo EDE approval found for maridebart cafraglutide (MariTide); an investigational medicine, not marketed in the UAEDetails →source2026-09-29
United KingdomNot approvedMaridebart cafraglutide has no UK licenceDetails →source2026-09-29
United StatesNot approvedInvestigational; Amgen is running Phase 3 trials (MARITIME programme) and no FDA approval or filing has been reportedDetails →source2026-09-29

Who makes it

Recent history

  1. 2025-06-23

    MariTide phase 2 trial: up to about 16% weight loss at 52 weeks with monthly dosing

Full timeline →

Related molecules

TirzepatideSemaglutideRetatrutide

Sources (46)

  1. 01Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 TrialNew England Journal of Medicine (PubMed) · 2025-06-23 · accessed 2026-09-29
  2. 02A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settingsNature Metabolism (PubMed) · 2024-02 · accessed 2026-09-29
  3. 03Evaluation of Maridebart Cafraglutide in Adult Participants Without Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (MARITIME-1, NCT06858839)ClinicalTrials.gov · 2025-03-05 · accessed 2026-09-29
  4. 04Efficacy and Safety of Maridebart Cafraglutide in Adult Participants With Type 2 Diabetes Mellitus Who Have Obesity or Are Overweight (MARITIME-2, NCT06858878)ClinicalTrials.gov · 2025-03-05 · accessed 2026-09-29
  5. 05Amgen reports second quarter 2026 financial resultsAmgen (PR Newswire) · 2026-08-04 · accessed 2026-09-29
  6. 06A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings (full text)Nature Metabolism (PubMed Central) · 2024-02 · accessed 2026-09-29
  7. 07Discovery of AMG 133, a Glucose-Dependent Insulinotropic Polypeptide Receptor Antagonist and Glucagon-Like Peptide 1 Receptor Agonist Antibody-Drug Conjugate for the Treatment of ObesityJournal of Medicinal Chemistry (PubMed) · 2026-04-23 · accessed 2026-09-29
  8. 08WEGOVY (semaglutide) injection / tablets - Prescribing Information (sections 12.1 Mechanism of Action, 12.2 Pharmacodynamics, 12.3 Pharmacokinetics)Novo Nordisk (DailyMed, U.S. National Library of Medicine) · 2026-06-18 · accessed 2026-09-29
  9. 09Semaglutide lowers body weight in rodents via distributed neural pathwaysJCI Insight (PubMed) · 2020-03-26 · accessed 2026-09-29
  10. 10The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesityDiabetes, Obesity and Metabolism (PubMed) · 2021-03 · accessed 2026-09-29
  11. 11The Effect of AMG 133 on Gastric Emptying (NCT07429032)ClinicalTrials.gov · 2026-02-24 · accessed 2026-09-29
  12. 12Results from Amgen's phase 2 obesity study of monthly MariTide presented at the American Diabetes Association 85th Scientific SessionsAmgen · 2025-06-23 · accessed 2026-09-29
  13. 13Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity (MARITIME-CV, NCT07037433)ClinicalTrials.gov · 2025-06-25 · accessed 2026-09-29
  14. 14ARTG keyword search for 'maridebart' (no matching results)Therapeutic Goods Administration (TGA) · 2026-09-29 · accessed 2026-09-29
  15. 15Prescription medicines under evaluation (last updated 21 September 2026)Therapeutic Goods Administration (TGA) · 2026-09-21 · accessed 2026-09-29
  16. 16Access pathways for unapproved therapeutic goodsTherapeutic Goods Administration (TGA) · 2025-10 · accessed 2026-09-29
  17. 17Dados abertos: registro de medicamentos (DADOS_ABERTOS_MEDICAMENTOS.csv)Agência Nacional de Vigilância Sanitária (Anvisa) · 2026-09-29 · accessed 2026-09-29
  18. 18Drug Product Database API: active-ingredient search for maridebart-cafraglutideHealth Canada (Drug Product Database) · 2026-09-29 · accessed 2026-09-29
  19. 19Drug and Health Product Submissions Under Review: New drug submissions under review (list current as of 2026-08-31)Health Canada · 2026-08-31 · accessed 2026-09-29
  20. 20Think twice before injecting peptides bought online: unauthorized products can seriously harm you (RA-81874)Health Canada · 2026-04-09 · accessed 2026-09-29
  21. 21CDE public register of accepted drug applications (受理品种目录浏览)Center for Drug Evaluation (CDE), NMPA · 2026-09-29 · accessed 2026-09-29
  22. 22Drug Administration Law of the PRC (中华人民共和国药品管理法)National Medical Products Administration (NMPA) · 2019-08-26 · accessed 2026-09-29
  23. 23Union Register of medicinal products for human useEuropean Commission · 2026-09-29 · accessed 2026-09-29
  24. 24Applications for new human medicines under evaluation by the CHMP (September 2026)European Medicines Agency · 2026-09-04 · accessed 2026-09-29
  25. 25Directive 2001/83/EC on the Community code relating to medicinal products for human use (consolidated text, 1 January 2025)European Union (EUR-Lex) · 2025-01-01 · accessed 2026-09-29
  26. 26Manufacturing and marketing of unapproved drug products containing Enclomiphene and its combinations (sets out the New Drugs rule for unapproved products)Central Drugs Standard Control Organisation (CDSCO) · 2026-08-10 · accessed 2026-09-29
  27. 27CDSCO Subject Expert Committee (SEC) recommendations index (records reviewed 2015 to September 2026)Central Drugs Standard Control Organisation (CDSCO) · 2026-09-23 · accessed 2026-09-29
  28. 28Approved new drugs list (Japanese), fiscal 2026 to date, covering approvals from May to September 2026 (承認品目一覧（新医薬品）)Pharmaceuticals and Medical Devices Agency (PMDA) · 2026-09 · accessed 2026-09-29
  29. 29Approved new drugs list (Japanese), April 2025 to March 2026 (承認品目一覧（新医薬品：2025年4月～2026年3月）)Pharmaceuticals and Medical Devices Agency (PMDA) · 2026-03 · accessed 2026-09-29
  30. 30List of Approved Drugs, April 2004 to February 2026 (new drugs)Pharmaceuticals and Medical Devices Agency (PMDA) · 2026 · accessed 2026-09-29
  31. 31Prescription drug package insert and review report search (医療用医薬品 添付文書等情報検索)Pharmaceuticals and Medical Devices Agency (PMDA) · 2026-09-29 · accessed 2026-09-29
  32. 32Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (PMD Act), consolidated textDigital Agency (e-Gov Law Search) · 2026-05-21 · accessed 2026-09-29
  33. 33Registros sanitarios de medicamentos alopáticos expedidos 2026COFEPRIS (Comisión Federal para la Protección contra Riesgos Sanitarios) · 2026-08-04 · accessed 2026-09-29
  34. 34Listados de registros sanitarios de medicamentos (visor y listas anuales)COFEPRIS (Comisión Federal para la Protección contra Riesgos Sanitarios) · 2025-08-21 · accessed 2026-09-29
  35. 35Solicitudes de medicamentos (excepto genérico y biocomparable) ingresadas en 2026COFEPRIS (Comisión Federal para la Protección contra Riesgos Sanitarios) · 2026-08-31 · accessed 2026-09-29
  36. 36Alerta sanitaria: comercialización ilegal de productos con tirzepatida sin registro sanitarioCOFEPRIS (Comisión Federal para la Protección contra Riesgos Sanitarios) · 2026-02-09 · accessed 2026-09-29
  37. 37Data sheets index (medicines with consent to be distributed in New Zealand)Medsafe (New Zealand Medicines and Medical Devices Safety Authority) · 2026-09-29 · accessed 2026-09-29
  38. 38Medicines Act 1981 (version as at 10 July 2026)New Zealand Parliamentary Counsel Office · 2026-07-10 · accessed 2026-09-29
  39. 39Consumer advisory: Unapproved peptide products health warningMedsafe (New Zealand Medicines and Medical Devices Safety Authority) · 2026-05-21 · accessed 2026-09-29
  40. 40Pharmaceutical licensing and drug registration in the UAE (Federal Decree-Law 38 of 2024)Kayrouz and Associates · 2026-03-18 · accessed 2026-09-29
  41. 41Federal Decree-Law No. (38) of 2024 on Medical Products, the Pharmacy Profession and Pharmaceutical Establishments (Arabic text)Emirates Drug Establishment (EDE) · 2024-10-01 · accessed 2026-09-29
  42. 42Legislations (Federal Decree-Law 38/2024 and other instruments)Emirates Drug Establishment (EDE) · 2026-09-29 · accessed 2026-09-29
  43. 43Find product information about medicines (MHRA Products register)Medicines and Healthcare products Regulatory Agency (MHRA) · 2026-09-25 · accessed 2026-09-29
  44. 44The Human Medicines Regulations 2012, regulation 46 (prohibition on sale or supply of unauthorised medicinal products)UK Government (legislation.gov.uk) · 2012 · accessed 2026-09-29
  45. 45Borderline products: how to tell if your product is a medicineMedicines and Healthcare products Regulatory Agency (MHRA) · 2026-07-02 · accessed 2026-09-29
  46. 46Development & Approval Process | DrugsU.S. Food and Drug Administration · 2022-08-08 · accessed 2026-09-29