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Amycretin

Amycretin (Zenagamtide)

Novo Nordisk's investigational single-molecule GLP-1/amylin receptor agonist, now called zenagamtide in newer pipeline materials. Both oral and injectable forms are in development.

Reviewed June 14, 2026·12 min read·8 citations·Not approvedPhase 3 program
On this page

At a glance

Amycretin is Novo Nordisk's investigational single-molecule GLP-1 and amylin receptor agonist. Newer Novo materials call it zenagamtide. The trend fit is strong: it takes the same GLP-1 + amylin logic behind CagriSema, but packages both activities into one molecule, with both injectable and oral development.

Animal studiesModerateMechanistic program

Novo has presented GLP-1/amylin receptor data, but the public evidence base is dominated by early human trials rather than independent animal replication.

Human evidenceModerate~530 participants

Published Phase 1 oral and Phase 1b/2a subcutaneous trials show strong early weight-loss signals, and a 262-participant Phase 2b type 2 diabetes trial presented at ADA 2026 met its A1C and body-weight endpoints. Pivotal Phase 3 results are not available.

Safety dataLimitedEarly-phase trials

Adverse events are mostly gastrointestinal and consistent with GLP-1/amylin biology, but exposure is short and early-phase.

How are these scores calculated?

New research, delivered clearly

When new studies publish or clinical trials report results, we'll break them down in plain language.

Quick facts

Current name
Zenagamtide
Legacy name
Amycretin
Mechanism
Unimolecular GLP-1 + amylin agonist
Routes
Subcutaneous and oral development
FDA status
Not approved
Developer
Novo Nordisk

Amino acid sequence

Proprietary unimolecular GLP-1 and amylin receptor agonist

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]

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.

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 program. It also has the main early-stage caveat: impressive Phase 1 and Phase 2 data can fail to generalize.

Peptide Garden evidence assessment, June 2026

Research timeline

  1. 2025Human study

    Oral Phase 1 data published

    The first-in-human Lancet paper reported up to 13.1% weight loss at 12 weeks in the highest oral amycretin cohort.

  2. 2025Human study

    Subcutaneous Phase 1b/2a data published

    Once-weekly subcutaneous amycretin showed estimated weight loss up to 24.3% at 36 weeks in a small early-phase trial.

  3. 2026Human study

    Phase 2b type 2 diabetes readout at ADA

    A 262-participant, 36-week Phase 2b trial of once-weekly subcutaneous zenagamtide (0.4-40 mg) met its A1C and body-weight endpoints, with up to 14.6% weight loss and up to 1.71-point A1C reduction at 40 mg.

  4. 2026Human study

    Phase 3 program advances

    Novo initiated the subcutaneous obesity Phase 3 program in Q1 2026 and plans to start a Phase 3 type 2 diabetes program in H2 2026.

Key clinical trials

2025·Phase 1, double-blind, randomized, placebo-controlled·n=144Moderate quality

First-in-human oral amycretin

Overweight or obesity

Oral amycretin reached up to 13.1% body-weight reduction at 12 weeks in the highest-dose oral cohort versus about 1% with placebo.

2025·Randomized, placebo-controlled early-phase study·n=125Moderate quality

Subcutaneous amycretin Phase 1b/2a

Overweight or obesity

Once-weekly subcutaneous amycretin produced estimated mean body-weight reductions of 24.3% at 60 mg and 22.0% at 20 mg over 36 weeks.

2026·Randomized, double-blind, placebo-controlled, dose-finding Phase 2b trial·n=262Moderate quality

Zenagamtide Phase 2b in type 2 diabetes (ADA 2026)

Type 2 diabetes

Over 36 weeks in 262 adults (baseline A1C 7.8%, ~219 lb), once-weekly subcutaneous zenagamtide across 0.4-40 mg met its A1C and body-weight endpoints. At 40 mg, A1C fell up to 1.71 percentage points and body weight up to 14.6%, with up to 89.1% reaching A1C below 7% (versus a 0.14-point A1C reduction and 2.1% weight loss on placebo). GI adverse events were mostly mild to moderate.

What the evidence shows

Does amycretin produce major weight loss?

Promising but not yet proven in pivotal trials. Subcutaneous amycretin showed 22.0-24.3% estimated weight loss at 36 weeks in a small Phase 1b/2a study.

Some supporting evidence

Is amycretin an oral GLP-1/amylin candidate?

Yes. The first-in-human oral trial showed up to 13.1% weight loss at 12 weeks, but larger and longer Phase 3 data are needed.

Some supporting evidence

Does amycretin improve blood sugar in type 2 diabetes?

Promising but not yet definitive. A 262-participant Phase 2b trial presented at ADA 2026 met its A1C and body-weight endpoints: at 40 mg, A1C fell up to 1.71 points and weight up to 14.6%, with up to 89.1% reaching A1C below 7% (versus a 0.14-point A1C reduction and 2.1% weight loss on placebo). A Phase 3 type 2 diabetes program is planned for H2 2026.

Some supporting evidence

Is amycretin the same as CagriSema?

No. CagriSema combines semaglutide and cagrilintide as two molecules. Amycretin is designed as a single molecule with both GLP-1 and amylin receptor activity.

Not yet demonstrated

Is amycretin FDA-approved?

No. Amycretin, now called zenagamtide in newer Novo materials, is investigational.

Not yet demonstrated

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.

Amycretin's early efficacy numbers are attention-grabbing, but the safety grade stays limited until Phase 3 exposes many more people for much longer.

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: the subcutaneous obesity Phase 3 program began in Q1 2026, and a Phase 3 type 2 diabetes program is planned for H2 2026 following the Phase 2b readout presented at ADA 2026.[5][6][7][4]

For athletes, it should be treated as prohibited under WADA S0 because it is an unapproved pharmacological substance.[8]

Comparisons

Profile Mechanism Why it matters
Amycretin / zenagamtide Single-molecule GLP-1 + amylin Oral and injectable development; strong early weight-loss signal
CagriSema Semaglutide + cagrilintide Two-molecule GLP-1 + amylin combination with Phase 3 data
Cagrilintide Amylin analogue Standalone amylin pathway and CagriSema component
Retatrutide GIP + GLP-1 + glucagon Alternative next-generation metabolic strategy

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.

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]
    Novo Nordisk. “AMAZE 1 Phase 3 study of subcutaneous NNC0487-0111.” 2026. LinkRCT

    ClinicalTrials.gov record for Phase 3 obesity development. Results not yet available.

  8. [8]
    World Anti-Doping Agency. “The 2026 Prohibited List.” 2026. LinkReview

    Used for S0 non-approved-substance regulatory context.

Medical disclaimer

Peptide Garden is an educational resource, not a medical provider. This page is informational and does not constitute medical advice. Amycretin/zenagamtide is investigational and should not be used outside regulated clinical trials or approved medical pathways.