Amycretin
Evidence: B — Meaningful Human EvidenceMetabolic / Weight Management
Evidence Snapshot
What this grade covers
SC obesity Phase 1b/2a and both-route Phase 1 FIH safety/PK are peer-reviewed; T2D Phase 2 glycemic/safety data is now peer-reviewed, but T2D weight-loss figures and the SC obesity efficacy figures remain early/mid-phase, short-duration (36 weeks or less) evidence -- not yet Phase 3.
Regulatory Context
Amycretin (zenagamtide) is investigational. No approval was identified in the verified searches used for this review in any jurisdiction. Phase 3 obesity trials (AMAZE-1, AMAZE-12) have begun enrolling/launched but have not yet reported results.
Research Takeaway
Amycretin (also known by the confirmed alias Zenagamtide) is a single-molecule (unimolecular) peptide that acts as an agonist at the GLP-1 receptor, the amylin receptor, and the calcitonin receptor.
Evidence boundary: This corrects an earlier dual-receptor (GLP-1/amylin only) description; the calcitonin-receptor component is peer-reviewed-confirmed and must be included going forward.
See all 7 evidence claims →Quick Summary
Amycretin (confirmed alias: Zenagamtide) is a single-molecule (unimolecular) peptide that acts as an agonist at the GLP-1 receptor, the amylin receptor, and the calcitonin receptor. It has shown substantial body-weight reduction in a subcutaneous Phase 1b/2a obesity trial and significant HbA1c improvement in companion subcutaneous and oral Phase 2 trials in type 2 diabetes. It is investigational, with Phase 3 obesity trials underway. Amycretin is a single molecule and is not the same as CagriSema or any cagrilintide+semaglutide co-administration regimen.
Mechanism & Research Overview
Amycretin (also known by the confirmed alias Zenagamtide) is a single-molecule (unimolecular) peptide that acts as an agonist at the GLP-1 receptor, the amylin receptor, and the calcitonin receptor, per two 2026 peer-reviewed phase 2 trials. This is a single molecule and must not be described as, or conflated with, CagriSema or any cagrilintide-plus-semaglutide co-administration regimen.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Amycretin (also known by the confirmed alias Zenagamtide) is a single-molecule (unimolecular) peptide that acts as an agonist at the GLP-1 receptor, the amylin receptor, and the calcitonin receptor.
Does not establish
Evidence boundary: This corrects an earlier dual-receptor (GLP-1/amylin only) description; the calcitonin-receptor component is peer-reviewed-confirmed and must be included going forward.
Sources: 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; 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
Supported
Amycretin/Zenagamtide is administered and studied as a single molecule. It is not the same as, and its evidence must not be used to describe, CagriSema (a fixed-dose cagrilintide/semaglutide co-formulation) or any other cagrilintide+semaglutide co-administration regimen.
Sources: Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study; 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
Supported
In a Phase 1b/2a dose-escalation RCT, SC amycretin produced placebo-adjusted body-weight reductions ranging from approximately 9.7% (lowest dose, 20 weeks) to 24.3% (highest dose, 36 weeks) in adults with overweight or obesity without diabetes.
Does not establish
Evidence boundary: Integrity status of this source is not yet independently re-confirmed via direct PubMed/Crossref record fetch -- carry this caveat until confirmed. Do not present as a durable/long-term outcome beyond 36 weeks.
Supported
In two companion Phase 2 RCTs (SC once-weekly and oral once-daily), amycretin/zenagamtide significantly improved HbA1c from baseline at week 36 in adults with type 2 diabetes: SC doses of 0.4-40mg reduced HbA1c by 0.9-1.7 percentage points from a baseline of 7.8%; oral doses of 6-50mg reduced HbA1c by 0.9-1.4 percentage points from a baseline of approximately 7.9-8.1%, versus placebo.
Does not establish
Evidence boundary: Weight-loss figures for this T2D population were NOT reported in either paper's abstract and are not frozen from this source.
Sources: 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; 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
Supported
A company announcement describes weight-loss reductions of up to 14.5% (SC) and 10.1% (oral) at week 36 in the same T2D trial population; this has not been independently confirmed in the peer-reviewed publications reviewed for this report.
Does not establish
Evidence boundary: Company-reported only; do not present as peer-reviewed-confirmed.
Supported
Across amycretin/zenagamtide's published trials, gastrointestinal adverse events were the most frequently reported, generally mild-to-moderate. In the T2D SC trial, 8% of participants had a serious adverse event, distributed across all dose groups and placebo, with no deaths. In the T2D oral trial, GI adverse events occurred in 26-47% of participants by dose, with 7 serious adverse events among zenagamtide recipients and none among placebo, no deaths. In the earlier both-route Phase 1 study, 62% of 144 participants had a treatment-emergent adverse event, all mild-to-moderate and GI-predominant.
Does not establish
Evidence boundary: Do not conflate the AE profiles of these three distinct trial populations.
Sources: 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; 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; 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
Supported
Amycretin/zenagamtide is investigational; no approval was identified in the verified searches used for this review in any jurisdiction. Phase 3 obesity trials (AMAZE-1, AMAZE-12) have begun enrolling/launched but have not yet reported results.
Sources: AMAZE-1: Phase 3 trial of zenagamtide (amycretin) in obesity; AMAZE-12: Phase 3 trial of zenagamtide (amycretin) for weight maintenance
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
Gastrointestinal adverse events are the most commonly reported side effects of amycretin/zenagamtide across its published trials, generally mild-to-moderate and dose-related. Trial-specific rates differ; do not blend across trials.Safety Consideration
Serious adverse events occurred in a minority of participants across dose groups and placebo in the T2D trials (8% overall in the SC trial; 7 events among zenagamtide recipients and none among placebo recipients in the oral trial), with no deaths reported. Distribution across specific SAE types was not extracted from accessible full text.Safety Consideration
Amycretin/zenagamtide's evidence to date comes from trials of 36 weeks or less; no long-term (multi-year) safety or durability data exists yet. Phase 3 trials (AMAZE program) have not yet read out.
Research Areas Being Studied
Research areas discussed on this page reflect the Metabolic / Weight Management category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- 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 (2026):
- 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 (2026):
- Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study (2025):
- 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 (2025):
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| 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 | 2026 | 186 randomized (156 zenagamtide, 30 placebo), type 2 diabetes | Companion oral-route paper to the SC T2D trial, describing zenagamtide/amycretin as a unimolecular peptide agonist of the GLP-1, amylin, and calcitonin receptors. HbA1c reduced by 0.9 percentage points (6mg, ETD vs placebo -0.5%, p=0.033) to 1.4 percentage points (50mg, ETD -1.09%, p<0.0001) from a baseline of approximately 7.9-8.1% at week 36.
| Gastrointestinal adverse events in 26% (6mg), 41% (25mg), and 47% (50mg) of participants vs 23% with placebo; 7 serious adverse events among zenagamtide recipients, none among placebo recipients; no deaths. | |
| 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 | 2026 | 262 of 915 screened adults randomly assigned (225 zenagamtide, 37 placebo; 261 exposed to treatment), type 2 diabetes, 83 hospital/clinic sites across 11 countries | Explicitly describes zenagamtide/amycretin as a unimolecular agonist of the GLP-1, amylin, AND calcitonin receptors (a triple-receptor mechanism, correcting the dual GLP-1/amylin framing used in earlier literature). HbA1c reduced by 0.9 percentage points (0.4mg dose) to 1.7 percentage points (40mg dose) from a baseline of 7.8%, versus placebo, at week 36 -- clinically meaningful and statistically significant at all tested doses.
| 21 of 261 participants (8%) had a serious adverse event, distributed across all dose groups and placebo (4 at 0.4mg, 3 at 1.5mg, 2 at 5mg, 5 at 10mg, 3 at 20mg, 1 at 40mg, 3 placebo); most adverse events were gastrointestinal, mild-to-moderate; no deaths. | |
| Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study | 2025 | Adults with overweight or obesity, non-diabetic | Placebo-adjusted body-weight reductions ranging from approximately 9.7% (lowest dose, 20 weeks) to 24.3% (highest dose, 36 weeks). Described by the authors as a unimolecular (single-molecule) GLP-1 and amylin receptor agonist, supporting its identity as distinct from co-administration products.
| Gastrointestinal adverse events, mild-to-moderate, dose-related; exact AE table not extracted from accessible full text. | |
| 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 | 2025 | 144 participants (Part A n=48, Part B n=36, Part C/D n=60), both subcutaneous and oral routes | First-in-human safety/tolerability/PK/PD study covering both the SC and oral routes.
| 364 treatment-emergent adverse events in 89 of 144 participants (62%), all mild-to-moderate and gastrointestinal-predominant. |
Animal / Cell / Preclinical Data
No Animal / Cell / Preclinical Data Listed Yet
This section will be updated as sources are added.
Regulatory Documents & Official Trial Registries
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| AMAZE-1: Phase 3 trial of zenagamtide (amycretin) in obesity | 2026 | Approximately 1,150 adults with obesity | Development-status only: Phase 3 obesity program registered, no results yet.
| ||
| AMAZE-12: Phase 3 trial of zenagamtide (amycretin) for weight maintenance | 2026 | Adults maintaining weight loss after diet-induced weight loss | Development-status only: Phase 3 weight-maintenance program registered, no results yet.
|
Review Articles / Secondary Sources
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Novo Nordisk phase 2 trial with amycretin reports significant weight loss and HbA1c reduction in type 2 diabetes (company-reported topline) | 2025 | Same NCT06542874 trial population as the peer-reviewed SC/oral papers | Company announcement (Nov 25, 2025) and EASD/ADA conference presentation reporting body-weight reductions of up to 14.5% (SC) and 10.1% (oral) at week 36 in the same T2D trial population. This figure has NOT been independently confirmed in the peer-reviewed publications reviewed for this project -- the peer-reviewed abstracts report HbA1c but not weight-loss figures. Treat as company-reported only, not peer-reviewed-confirmed. |
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published research and does not provide medical advice, a recommendation, or instructions for human use.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated .
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