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Amycretin
GLP-1 Analogs

Amycretin

Novo Nordisk

Amycretin (renamed zenagamtide in 2026 publications) is an experimental peptide that activates the GLP-1 receptor and the amylin receptor from a single molecule; the 2026 phase 2 papers describe it as an agonist of GLP-1, amylin and calcitonin receptors. Instead of combining two drugs, as cagrilintide plus semaglutide does, it builds incretin and amylin signaling into one long-acting agent. Amylin, a hormone co-secreted with insulin, promotes satiety and slows gastric emptying by routes that complement GLP-1. Novo Nordisk is developing it in two forms, a once-weekly subcutaneous injection and a once-daily oral tablet. In a phase 1b/2a study in 125 adults with overweight or obesity, once-weekly injections produced estimated mean weight changes of −24.3% at 60 mg and −22.0% at 20 mg after 36 weeks, versus about −1% to +2% on placebo. Gastrointestinal adverse events were the most common, and many participants withdrew. In 2026, two 36-week phase 2 trials in type 2 diabetes reported HbA1c reductions of 0.9–1.7% with weekly injections and 0.9–1.4% with daily tablets. These are early, mostly company-run studies with limited numbers of participants. Amycretin is investigational and not approved by any regulator; larger phase 3 trials are needed to confirm its benefit and long-term safety. Products sold online under its name are unregulated, and JAMA has reported on a black market for it. This page is an educational reference, not a guide to obtaining or using it.

Specifications

Origin / ManufacturerSynthetic peptide co-agonist
Active Components
Amycretin
StorageNot established (investigational)
Shelf LifeNot established (investigational)
Form FactorSubcutaneous injection and oral tablet (both under development)

Clinical Evidence

Oral, first-in-human phase 1 (Gasiorek et al., Lancet 2025; 144 adults with overweight or obesity): single and multiple ascending doses, including 12 weeks of escalation up to 100 mg daily. Treatment-emergent adverse events occurred in 62% of participants, all mild or moderate and dose-dependent; most were gastrointestinal. Weight change was an exploratory endpoint.

Clinical report reference

Subcutaneous phase 1b/2a (Dahl et al., Lancet 2025; 125 adults with overweight or obesity): estimated mean weight change was −24.3% with 60 mg versus −1.1% on placebo at week 36, −22.0% with 20 mg (week 36), −16.2% with 5 mg (week 28) and −9.7% with 1.25 mg (week 20). Gastrointestinal events were common, mostly mild to moderate, and many participants withdrew.

Clinical report reference

Subcutaneous phase 2 in type 2 diabetes (Mora et al., Lancet 2026; 262 adults on metformin with or without an SGLT2 inhibitor): after 36 weeks, HbA1c fell by 0.9% (0.4 mg) to 1.7% (40 mg) from a baseline of 7.8%; the treatment difference versus placebo ranged from −0.77 to −1.56 percentage points. Most adverse events were gastrointestinal and mild to moderate.

Clinical report reference

Oral phase 2 in type 2 diabetes (Mora et al., Lancet 2026; 186 adults): after 36 weeks, HbA1c fell by 0.9%, 1.3% and 1.4% with 6, 25 and 50 mg daily (−0.5 to −1.09 points versus placebo). Gastrointestinal adverse events occurred in 26–47% of zenagamtide groups versus 23% on placebo.

Clinical report reference

These are phase 1 and phase 2 studies sponsored by the developer; phase 3 data on efficacy, durability and long-term safety are not yet published.

Clinical report reference

Frequently Asked Questions

Sources & References

Every clinical claim on this page traces to a primary peer-reviewed source.

  1. 1Gasiorek A, Heydorn A, Gabery S, et al.. 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. Lancet. 2025;406(10499):135-148. doi:10.1016/S0140-6736(25)01176-6 PMID:40550229
  2. 2Dahl K, Toubro S, Dey S, et al.. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study. Lancet. 2025;406(10499):149-162. doi:10.1016/S0140-6736(25)01185-7 PMID:40550231
  3. 3Mora P, Aroda VR, Asong M, et al.. 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. Lancet. 2026;408(10555):621-635. doi:10.1016/S0140-6736(26)01248-1 PMID:42532080
  4. 4Mora P, Aroda VR, Asong M, et al.. 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. Lancet. 2026;408(10555):607-620. doi:10.1016/S0140-6736(26)01247-X PMID:42532079
  5. 5Kuhre RE, Ballarín-González B, Brand CL, et al.. The effect of amycretin, a unimolecular glucagon-like peptide-1 and amylin receptor agonist, on body weight and metabolic dysfunction in mice and rats. EBioMedicine. 2025;118:105862. doi:10.1016/j.ebiom.2025.105862 PMID:40706446
  6. 6Rubin R. Unapproved GLP-1 Drugs Retatrutide and Zenagamtide Sold Online Are No Bargain. JAMA. 2026. doi:10.1001/jama.2026.20514 PMID:42853576

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Peptides Academy Editorial

Editorial Team

All clinical claims cross-checked against primary sources. Read our editorial policy →

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Reviewed by Peptides Academy EditorialEditorial Team

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