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Amylin analogue

Amycretin

Also called Zenagamtide, NNC0487-0111.

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.

Amycretin 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.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.

Last verified 2026-09-29 · how we verify

Placeholder

No experimental structure or sequence to show — abstract placeholder, not a structure

No PDB structure and no amino-acid sequence is recorded for Amycretin on this site.

Acts on
GLP-1 receptor, Amylin receptors (calcitonin receptor with RAMP proteins), Calcitonin receptor
Taken as
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.
Half-life
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.[src]
Regulatory status
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.[src]
Phase 1b/2a weight change (obesity, subcutaneous)
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).[src]
Phase 2 HbA1c (type 2 diabetes)
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.[src]

Inside the body

What Amycretin does, step by step

Watch the 3D journey →
  1. 01Bloodstream

    Rides on albumin in the blood

    The molecule has a fatty tail that lets it stick loosely to a common blood protein called albumin. This keeps it from being cleared quickly. In people, it takes about 3.7 days for the body to clear half of it, which fits with the injection version being studied once a week.

    For experts

    A C18 diacid side chain on Lys37 (GLP-1 7-37 numbering) enables reversible albumin binding and a long systemic half-life; an Aib substitution in the N-terminal GLP-1 region stabilises against DPP-4. In a single-dose study in 42 adults, the geometric mean terminal half-life was 88.1 h with normal kidney function and 94.0 to 112.8 h across mild to end-stage kidney impairment, with median time to peak concentration of 36 to 48 h. Animal data: preclinical terminal half-lives (harmonic means) rose with species size: 3.65 h in mice (subcutaneous), 29.7 h in monkeys (subcutaneous) and 54.1 h in minipigs (intravenous).[src][src]

  2. 02Brain

    Reaches appetite-control areas of the brain (animal data)

    In mice, a glowing tagged copy of the molecule was seen in brain areas that help control hunger and fullness. This was shown in animals only. It has not been shown the same way in people.

    For experts

    Animal-only: after a single dose of a fluorescently labelled version (amycretin-VT750) in mice, signal was seen in the circumventricular organs (area postrema, median eminence, vascular organ of the lamina terminalis, subfornical organ) and in blood-brain-barrier-protected regions including the arcuate nucleus, nucleus of the solitary tract and dorsal motor nucleus of the vagus. Semaglutide-VT750 was detected in the same regions. Amylin receptors sit in the hypothalamus and dorsal vagal complex of the hindbrain (review). Direct human brain-distribution data for amycretin were not found.[src][src]

  3. 03Brain

    Switches on GLP-1, amylin and calcitonin receptors; eating falls

    One molecule turns on the GLP-1 receptor and the amylin receptor, both linked to feeling full. In rats it cut how much they ate by almost half. In people, body weight fell in trials, but how much of that is due to appetite has not been fully measured.

    For experts

    In cell-based assays amycretin activated human, mouse and rat GLP-1, amylin and calcitonin receptors. Animal-only: in diet-induced obese rats, 21 days of treatment reduced total energy intake by 47% and body weight by 18% while energy expenditure was maintained. Human data: in the phase 1b/2a study, body-weight change was -24.3% versus -1.1% with placebo at week 36 at the highest dose tested, with high discontinuation. A 2026 review describes engagement of hindbrain-mediated satiety pathways and delayed gastric emptying as the proposed mechanisms, but appetite and food-intake measures in people are not reported in the primary papers reviewed here.[src][src][src]

  4. 04Stomach

    May slow how fast the stomach empties

    Amylin and GLP-1 are both known to slow how quickly food leaves the stomach, which adds to feeling full. Whether amycretin does this in people has been studied, but published results were not found.

    For experts

    Delayed gastric emptying is a recognised action of amylin and of GLP-1 receptor agonists as a class, and a 2026 review attributes it to amycretin. Novo Nordisk ran a phase 1 study (NCT06461039, completed 2025) whose primary aim was an interaction with an oral contraceptive and which also measured gastric emptying (paracetamol absorption after a standard meal); no results are posted on ClinicalTrials.gov and no publication was found, so an amycretin-specific human effect size is not stated.[src][src][src]

  5. 05Pancreas

    Helps the pancreas control blood sugar

    GLP-1 helps the pancreas release insulin when blood sugar is high, and amylin turns down a hormone called glucagon that raises blood sugar. Amycretin was designed to do both. In adults with type 2 diabetes it lowered blood sugar.

    For experts

    GLP-1 receptor agonism stimulates insulin secretion and lowers glucagon in a glucose-dependent manner (label of the reference GLP-1 receptor agonist semaglutide); amylin suppresses glucagon secretion (review). These pancreatic actions are class-level mechanisms and were not isolated for amycretin in the sources reviewed. The clinical effect is measured in the phase 2 diabetes trials.[src][src][src]

  6. 06Liver

    Fatty liver and insulin sensitivity improved in rodents

    In rats fed a fattening diet, amycretin improved how well the body responds to insulin and reduced fat build-up in the liver. These findings come from animals only. Whether the same happens in people has not been shown.

    For experts

    Animal-only: in diet-induced obese rats treated for 35 days, a hyperinsulinaemic-euglycaemic clamp showed higher glucose infusion rates than vehicle, and amycretin improved histological hallmarks of MASLD, primarily by reducing steatosis. No human liver-outcome data for amycretin were found.[src]

  7. 07Bloodstream

    Lowers HbA1c in adults with type 2 diabetes

    In a 36-week trial in adults with type 2 diabetes, both the weekly injection and the daily tablet lowered long-term blood sugar (HbA1c) more than placebo. Most side effects were stomach and gut problems.

    For experts

    In a 36-week, placebo-controlled phase 2 trial (NCT06542874; subcutaneous and oral parts reported separately) in adults with type 2 diabetes on metformin (baseline HbA1c about 7.8 to 8.1%), subcutaneous zenagamtide lowered HbA1c by 0.9% at the lowest dose up to 1.7% at the highest dose (estimated treatment difference versus placebo -0.77 to -1.56 percentage points); oral zenagamtide lowered HbA1c by 0.9% to 1.4% (ETD -0.5 to -1.09). Company topline figures reported body-weight loss of up to 14.5% (subcutaneous, versus 2.6% with placebo) and 10.1% (oral, versus 2.5% with placebo).[src][src][src]

For experts

The detail

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

Known safety signals

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

Around the world

Is Amycretin legal where you live?

CountryStatusWhat it meansVerified
AustraliaNot approvedInvestigational only. No amycretin product is on the ARTG and no application appears on the TGA's evaluation list.Details →source2026-09-29
BrazilNot approvedAmycretin is an investigational drug with no Brazilian registrationDetails →source2026-09-29
CanadaNot approvedAmycretin is an investigational drug with no Health Canada authorisationDetails →source2026-09-29
ChinaNot approvedNot approved in China; Novo Nordisk has only clinical-trial applications on file.Details →source2026-09-29
European UnionNot approvedInvestigational; no EU marketing authorisation and no application under evaluationDetails →source2026-09-29
IndiaNot approvedNot approved in India; Novo Nordisk's amycretin (code NNC0487-0111) is only in CDSCO-permitted Phase III trialsDetails →source2026-09-29
JapanNot approvedNo marketing approval in Japan; the investigational amylin and GLP-1 agonist amycretin does not appear in PMDA's approved-drug lists to September 2026Details →source2026-09-29
MexicoNot approvedNot registered in Mexico; amycretin is an investigational Novo Nordisk medicineDetails →source2026-09-29
New ZealandNot approvedAmycretin is an investigational medicine with no Medsafe consent in New ZealandDetails →source2026-09-29
United Arab EmiratesNot approvedNo EDE approval found for amycretin; an investigational medicine, not marketed in the UAEDetails →source2026-09-29
United KingdomNot approvedInvestigational medicine with no UK licenceDetails →source2026-09-29
United StatesNot approvedNo FDA approval or filing; Novo Nordisk now calls it zenagamtide and has started Phase 3 trialsDetails →source2026-09-29

Who makes it

Related molecules

Cagrilintide (and CagriSema)SemaglutidePramlintideEloralintide

Sources (52)

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