Amycretin

Research Reagent · Laboratory Use Only

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.

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.

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).
  • 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 June 2026. Phase 3 obesity programme initiated Q1 2026; Phase 3 for type 2 diabetes planned H2 2026. No compounding eligibility.

Clinical Research Parameters
1 trial2 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.

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.

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

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.