Amycretin

At a glance

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What is amycretin?

Amycretin is an investigational metabolic peptide from Novo Nordisk. The newer pipeline name is zenagamtide, but amycretin is still the name used in the published early clinical papers and most public discussion.^[5]

The key design idea is "unimolecular" GLP-1 + amylin agonism. Instead of giving semaglutide and cagrilintide as two molecules, as in CagriSema, amycretin is designed as a single molecule that engages both pathways.

That is why the oral data attracted attention. If a peptide-based GLP-1/amylin agonist can work orally, it could offer a different kind of convenience than weekly injections. The evidence is not mature enough to treat it as proven, but the early signal is unusually strong for a first-in-human oral obesity candidate.^[1]

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How it works

Amycretin combines two appetite and metabolic pathways in one molecule:

• GLP-1 receptor agonism: appetite suppression, glucose-dependent insulin secretion, glucagon suppression, and delayed gastric emptying.
• Amylin receptor agonism: complementary satiety signaling, glucagon suppression, and additional post-meal appetite regulation.

The hypothesis is that hitting both pathways with one molecule can produce weight loss comparable to more complex combinations while preserving flexible development routes: once-weekly injection and once-daily oral dosing.^[1][2]

Name mapping

You may see several names for the same general program:

• Amycretin: older public and publication name.
• Zenagamtide: newer Novo Nordisk pipeline name.
• NNC0487-0111: development code used in trial registries.
• NN9487 / NN9490: Novo internal asset codes used across obesity and diabetes materials.

For user-facing clarity, this profile uses Amycretin in the title because that is the common search name, while noting zenagamtide as the current Novo name.

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What the research says

Amycretin has the profile of a real next-wave metabolic candidate: strong early weight-loss signals, oral and injectable paths, a positive Phase 2b diabetes readout, and a Phase 3 programme that has grown considerably. It also has the main early-stage caveat, and the size of the programme does not change it: impressive Phase 1 and Phase 2 data can fail to generalize, and none of these Phase 3 trials has reported anything yet.

Research timeline

Key clinical trials

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What the evidence shows

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Safety & side effects

The published amycretin studies describe a safety and tolerability pattern broadly consistent with GLP-1 and amylin receptor agonism. Gastrointestinal events were the main category, and most were mild to moderate in severity in the early studies.^[1][2]

What is still unknown:

• Long-term safety beyond early development windows.
• Rare-event safety in large, diverse populations.
• Comparative tolerability against semaglutide, tirzepatide, CagriSema, and retatrutide.
• Cardiovascular outcomes.
• Which formulation, oral or injectable, will have the better efficacy/tolerability balance.

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Legal & regulatory status

Amycretin/zenagamtide is not FDA-approved, not available by prescription, and not compoundable. Novo Nordisk describes it as a Phase 3 development asset, not an available medicine.^[5][7][4]

What the Phase 3 programme actually covers

Novo's second-quarter 2026 investor presentation, published August 5, 2026, lays out a programme considerably broader than the one described in earlier materials.^[9] Two things are worth understanding about it.

First, the shape. The obesity trials are grouped under the name AMAZE and the diabetes trials under AMBITION. AMAZE spans general obesity, obesity in people with type 2 diabetes, obstructive sleep apnea, and knee osteoarthritis — the same "obesity plus a specific complication" pattern used by other late-stage obesity programmes, because showing benefit for a named condition is how a drug earns a label for it. AMBITION covers zenagamtide on its own, added to insulin, and compared head-to-head against semaglutide 1.0 mg. Separately, HF-POLARIS tests zenagamtide in heart failure on top of standard care — a direction that was not part of the public picture before this year. The oral formulation has its own Phase 3 trial, AMAZE 9, registered on July 22, 2026 with 950 participants over 76 weeks.^[8] Novo has guided to starting oral Phase 3 in the third quarter of 2026 and a subcutaneous cardiovascular outcomes trial in the fourth.

Second, and more important: none of this is evidence that the drug works. Launching a large Phase 3 programme is a commercial and strategic decision, made on Phase 2 data and business judgment. It signals confidence, not proof. Trial durations and endpoints described above come from a company timeline slide, which is why we describe them in general terms rather than quoting specifics. Every efficacy number on this page still comes from a Phase 1 or Phase 2 trial.

For athletes, it should be treated as prohibited under WADA S0 because it is an unapproved pharmacological substance.^[10]

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Comparisons

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Related content

Peptide

CagriSema Profile

The two-molecule GLP-1 + amylin combination that makes amycretin's single-molecule strategy easier to understand.

Peptide

Cagrilintide Profile

The long-acting amylin analogue driving much of the beyond-GLP-1 obesity pipeline conversation.

Peptide

Semaglutide Profile

The GLP-1 reference point for interpreting amycretin's dual GLP-1/amylin mechanism.

Peptide

Retatrutide Profile

A different next-generation metabolic strategy: triple GIP/GLP-1/glucagon agonism.

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References

1. [1]

   Gasiorek A, Heydorn A, Gabery S, Hjerpsted JB, 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. 406:135-148 DOI PubMedRCT

   First-in-human trial including oral amycretin. Early-phase and short duration, but important for oral formulation signal.

2. [2]

   Dahl 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 PubMedRCT

   Single-center Phase 1b/2a trial. Strong dose-response weight-loss signal but small sample, early phase, and high discontinuation context.

3. [3]

   Novo Nordisk. “Novo Nordisk's subcutaneous and oral amycretin data published in The Lancet and presented at ADA 2025.” 2025. LinkReview

   Company announcement summarizing Lancet publications and ADA presentation. Useful for program context, not independent evidence.

4. [4]

   Novo Nordisk. “Novo Nordisk's investigational zenagamtide shows significant A1C reductions with up to 14.6% weight loss in adults with type 2 diabetes — presented at ADA 2026.” 2026. LinkRCT

   Company release summarizing the 262-participant, 36-week Phase 2b dose-finding type 2 diabetes trial (0.4–40 mg once-weekly subcutaneous) presented at ADA 2026. Peer-reviewed publication pending.

5. [5]

   Novo Nordisk. “Novo Nordisk Annual Report 2025 — Innovation and therapeutic focus.” 2026. LinkReview

   Uses current Novo naming: zenagamtide, formerly amycretin; describes Phase 3 development in obesity and diabetes.

6. [6]

   Novo Nordisk. “Q1 2026 Investor Presentation.” 2026. LinkReview

   Corporate update describing AMAZE and AMBITION Phase 3 program timing and Phase 2 T2D summary metrics.

7. [7]

   ClinicalTrials.gov. “NCT07339423: AMAZE 1 — A Research Study Investigating How Well the Medicine NNC0487-0111 Helps People With Excess Body Weight Lose Weight.” 2026. LinkRegistered trial (no results)

   Registry record for the lead Phase 3 subcutaneous obesity trial. 1,150 participants, recruiting. A trial registration, not a result.

8. [8]

   ClinicalTrials.gov. “NCT07720271: AMAZE 9 — A Research Study Investigating How Well Zenagamtide Tablets Help People With Excess Body Weight Lose Weight.” 2026. LinkRegistered trial (no results)

   Registry record for the oral zenagamtide Phase 3 trial, first posted July 22, 2026. 950 participants, 76 weeks, primary endpoint body-weight change vs. placebo; not yet recruiting at the time of writing. A trial registration, not a result.

9. [9]

   Novo Nordisk. “Investor presentation, Second quarter of 2026.” 2026. LinkReview

   Corporate investor presentation dated August 5, 2026. Primary source for the AMAZE (obesity) and AMBITION (diabetes) Phase 3 architecture, the HF-POLARIS heart-failure trial initiated in Q2 2026, and Novo's guidance on oral Phase 3 initiation (Q3 2026) and a subcutaneous cardiovascular outcomes trial (Q4 2026). Trial designs come from a directional timeline slide and are described qualitatively here. Company-authored: useful for programme status, not independent evidence.

10. [10]

    World Anti-Doping Agency. “The 2026 Prohibited List.” 2026. LinkReview

    Used for S0 non-approved-substance regulatory context.

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