Metabolic/Weight

Amycretin

Research Reagent · Laboratory Use Only

Quick Answer

What does research show about amycretin for weight loss compared to semaglutide?

Amycretin (zenagamtide, NNC0385-0434) is a first-in-class unimolecular GLP-1 and amylin receptor dual agonist. In a Phase 1b/2 trial published in The Lancet (December 2024), subcutaneous amycretin produced approximately 22% mean body weight reduction versus approximately 10.6% with semaglutide 2.4 mg at 26 weeks. Phase 3 programmes for obesity (REDEFINE) are now enrolling as of 2026.

PMID39626360↗DOI10.1016/S0140-6736(24)02496-8↗⟳ Reconstitution Calculator
Scientific AbstractPMID 39626360 · 2025

Amycretin (NNC0385-0434; also known as zenagamtide) is a first-in-class, unimolecular, long-acting glucagon-like peptide-1 (GLP-1) and amylin receptor agonist developed by Novo Nordisk. 4 mg in adults with overweight or obesity over 26 weeks. 6% with semaglutide, representing a substantial differentiation from existing GLP-1 monotherapy.

Phase 3 programmes for obesity (REDEFINE series) are now enrolling as of Q1 2026. 1% achieving A1C <7% at 36 weeks in a Phase 2 dose-finding study (NCT06542874), presented at ADA 2026. Phase 3 for T2D is planned for H2 2026.

An oral formulation is also under development.

Source:10.1016/S0140-6736(24)02496-8
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Amycretin?

Amycretin (NNC0385-0434; also called zenagamtide in later-stage development) is a first-in-class, unimolecular GLP-1 and amylin receptor dual agonist developed by Novo Nordisk. Unlike CagriSema (a fixed-dose combination of two separate molecules: cagrilintide and semaglutide), amycretin is a single molecule designed to activate both the GLP-1 receptor and the amylin/calcitonin receptor simultaneously. It is under investigation for once-weekly subcutaneous and once-daily oral administration.

Mechanism of Action

Amycretin exploits the complementary and synergistic satiety pathways of two hormones:

  • GLP-1 receptor activation: Suppresses appetite via the hypothalamus and brainstem, slows gastric emptying, and enhances glucose-dependent insulin secretion.
  • Amylin receptor activation: Acts on the area postrema and brainstem to reduce meal size, slow gastric emptying, and suppress glucagon. Amylin works through different neural circuits than GLP-1, providing additive satiety signalling.

The dual agonism in a single molecule simplifies dosing and may achieve greater weight loss than GLP-1 monotherapy.

Observed Clinical Results

  • Phase 1b/2 (Lancet, December 2024): Subcutaneous amycretin 2.4 mg achieved ~22% mean body weight reduction vs ~10.6% with semaglutide 2.4 mg at 26 weeks in adults with obesity or overweight.
  • Phase 2 T2D (NCT06542874): Zenagamtide 40 mg SC once-weekly produced 14.6% weight loss and 89.1% of patients achieving A1C <7% at 36 weeks (ADA 2026 presentation). Now published as two companion papers in The Lancet (Aug 15, 2026; Mora P et al.): the subcutaneous arm (262 participants; PMID 42532080) reduced HbA1c by 0.9% (0.4 mg) to 1.7% (40 mg) at week 36 (placebo-adjusted up to -1.56%), and the once-daily oral arm (186 participants; PMID 42532079) reduced HbA1c by 0.9% (6 mg), 1.3% (25 mg) and 1.4% (50 mg), with up to 10.3% weight loss at 25 mg. Adverse events were mainly mild-to-moderate gastrointestinal events; no deaths occurred.
  • Oral formulation Phase 1: ~13.1% weight loss at 12 weeks with oral amycretin in early-phase data.
  • Phase 3 REDEFINE obesity programme: Enrolling as of Q1 2026.

Regulatory Status

Currently Investigational: no regulatory approval as of September 2026. Phase 3 obesity programme (AMAZE) initiated Q1 2026; Phase 3 for type 2 diabetes (AMBITION programme) planned H2 2026: no AMBITION trial registration had been confirmed as of September 29, 2026. No compounding eligibility.

Clinical Research Parameters
2 trials5 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters, not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT06542874 ↗
COMPLETEDPhase IIn=290

A Research Study to Look at How Subcutaneous Zenagamtide (Also Known as NNC0385-0434) Works in People With Type 2 Diabetes

A Phase 2, randomised, double-blind, dose-finding study evaluating subcutaneous zenagamtide (amycretin, NNC0385-0434) in adults with type 2 diabetes. The highest dose studied (40 mg) achieved up to 14.6% body weight loss and 89.1% of patients reaching HbA1c below 7% at 36 weeks. Results were presented at the American Diabetes Association Scientific Sessions (ADA 2026). Phase 3 development planned for H2 2026. Full results published September 2026 as two companion Phase 2 papers in The Lancet (Mora P et al., Lancet 2026;408:607-635): subcutaneous arm (n=262, randomised 6:1 to 0.4-40 mg or placebo) reduced HbA1c by 0.9%-1.7% from baseline 7.8% at week 36 (placebo-adjusted -0.77% to -1.56%); oral once-daily arm (n=186, 6/25/50 mg) reduced HbA1c by 0.9%/1.3%/1.4% (placebo-adjusted -0.5% to -1.09%), with up to 10.3% weight loss at 25 mg. Trial conducted at 83 sites in 11 countries; completed.

Study Interventions
Zenagamtide (NNC0385-0434), Placebo
Primary Endpoints
Change in HbA1c from baseline at 36 weeks; Percent change in body weight
Study Period
2024-01 → 2025-12
NCT07339423 ↗
RECRUITINGPhase IIIn=1,150

AMAZE 1: A Research Study Investigating How Well the Medicine Zenagamtide (NNC0487-0111) Helps People With Excess Body Weight Lose Weight

AMAZE-1 is a Phase 3, randomised, double-blind, placebo-controlled trial evaluating oral zenagamtide (amycretin, NNC0487-0111) tablets in approximately 1,150 adults with overweight or obesity, across 72 sites in 9 countries. AMAZE-1 is the first of Novo Nordisk's Phase 3 AMAZE program for amycretin/zenagamtide in obesity, following positive Phase 2 data in type 2 diabetes (up to 14.6% weight loss at 36 weeks, presented at ADA 2026). Results not yet reported as of this update.

Study Interventions
Zenagamtide (NNC0487-0111) oral tablet, Placebo
Primary Endpoints
Percent change in body weight from baseline
Study Period
2026-02-24 → 2029-08-21
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Amycretin is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 39626360) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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Research Articles

Amycretin in the Research Blog

Next-Generation GLP-1 Peptides 2026: 9 Emerging Compounds Beyond Semaglutide and Tirzepatide
Research Overview · 11 min read
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Amycretin vs Semaglutide: Is Novo's Dual GLP-1/Amylin Agonist the Next-Generation Incretin?
Compound Comparison · 9 min read
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Eloralintide vs Amycretin (2026): Selective Amylin vs Unimolecular Amylin/GLP-1 Agonist Data
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Amycretin vs Cagrilintide (2026): One Molecule vs CagriSema's Two-Drug Approach
Compound Comparison · 9 min read
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