Amycretin

Also known as zenagamtide

InvestigationalAHuman trial evidence What this means

Amycretin (now also called zenagamtide) is an investigational single-molecule peptide that activates both GLP-1 and amylin receptors. It has been studied in subcutaneous and oral forms in phase 1 and phase 2 randomized trials, and phase 3 trials are registered. It is not an approved medicine, and this entry is for research information only.

US status: Investigational
Evidence: Grade A
Half-life: Geometric mean terminal half-life of 88.1 hours after a single 0.3 mg subcutaneous dose in participants with normal renal function (94.0–112.8 hours with renal impairment)
Class: Unimolecular GLP-1 receptor and amylin receptor agonist (investigational)

Studied in: Appetite & body weight · Metabolic & insulin research · Class: Amylin analogues

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Key takeaways

Amycretin is a single molecule designed to act on GLP-1, amylin and calcitonin receptors ^3,5.
In a phase 1b/2a subcutaneous study, estimated mean body-weight change versus placebo was -24.3% versus -1.1% (60 mg, week 36) and -22.0% versus +1.9% (20 mg, week 36) ^2.
In 36-week phase 2 trials in type 2 diabetes, subcutaneous and oral forms both lowered HbA1c more than placebo at every dose tested ^3,4.
Gastrointestinal events were the most common adverse events, and the phase 1b/2a study reported a large number of withdrawals ^2.
Amycretin is not FDA-approved; it was renamed zenagamtide, and phase 3 trials, including a cardiovascular outcomes trial, were registered in 2026 ^3,6,7,8.

Development stage

Where Amycretin sits between laboratory work and regulatory approval.

Preclinical
Animal and cell work
Phase 1
First human safety studies
Phase 2
Early efficacy signal
Phase 3 (current)
Confirmatory trials
Approved
Cleared by a regulator

Stage comes from the regulatory record and ClinicalTrials.gov studies naming the compound (for compounds approved nowhere, only completed trials or trials with posted results count) (checked 2026-10-24). A registered trial is not a result.

Mechanism of action

Amycretin is a 68-amino-acid peptide with an average molecular weight of 7847 Da in which a GLP-1 receptor agonist portion and an amylin receptor agonist portion are connected by a linker of four glycine residues and one glutamic acid residue ⁵. It is acylated with a C18 diacid-based side chain on the GLP-1 portion, which the developers state enables reversible albumin binding and a long systemic half-life ⁵.

Receptor activity

In cell-based systems, amycretin activated human, mouse and rat GLP-1, amylin and calcitonin receptors ⁵. The 2026 phase 2 reports describe zenagamtide (formerly amycretin) as a unimolecular agonist of GLP-1, amylin and calcitonin receptors ³.

Animal findings

In diet-induced obese rats, 21 days of amycretin reduced total energy intake by 47% and lowered body weight by 18% relative to vehicle while energy expenditure was maintained ⁵. Insulin sensitivity improved during a hyperinsulinaemic euglycaemic clamp, and liver histology showed reduced steatosis ⁵. Amycretin reached brain areas involved in regulating food intake in mice ⁵.

Research overview

Human research

Amycretin has been studied as an oral tablet in a first-in-human phase 1 study in 144 participants ^1, as a once-weekly subcutaneous injection in a phase 1b/2a study in 125 participants with overweight or obesity ^2, and in two 36-week phase 2 dose-finding trials in type 2 diabetes using the subcutaneous (262 participants) and oral (186 participants) forms ^3,4. Phase 3 trials, including a cardiovascular outcomes trial, are registered ^6,7.

Animal research

In diet-induced obese mice and rats, amycretin reduced energy intake and body weight, improved insulin sensitivity and reduced liver steatosis ^5.

In-vitro research

Cell-based assays showed activation of human, mouse and rat GLP-1, amylin and calcitonin receptors ^5.

Key studies

Dahl et al., Lancet (2025)
Randomized, placebo-controlled phase 1b/2a, single centre, up to 36 weeks
Model: Humans (125 adults with overweight or obesity)
Estimated mean body-weight change was -24.3% vs -1.1% (60 mg, week 36), -22.0% vs +1.9% (20 mg, week 36), -16.2% vs +2.3% (5 mg, week 28) and -9.7% vs +2.0% (1.25 mg, week 20) ^2.
Mora et al., Lancet (subcutaneous) (2026)
Randomized, double-blind, placebo-controlled, dose-finding phase 2, 36 weeks
Model: Humans (262 adults with type 2 diabetes)
HbA1c change ranged from -0.9% (0.4 mg) to -1.7% (40 mg) from a mean baseline of 7.8%; treatment differences versus placebo ranged from -0.77 to -1.56 percentage points ^3.
Mora et al., Lancet (oral) (2026)
Randomized, double-blind, placebo-controlled, dose-finding phase 2, 36 weeks
Model: Humans (186 adults with type 2 diabetes)
HbA1c change was -0.9% (6 mg), -1.3% (25 mg) and -1.4% (50 mg) once daily; differences versus placebo were -0.5 to -1.09 percentage points ^4.
Gasiorek et al., Lancet (2025)
First-in-human, randomized, double-blind, placebo-controlled phase 1 (oral)
Model: Humans (144 adults with overweight or obesity)
364 treatment-emergent adverse events occurred in 89 of 144 participants (62%), all mild or moderate and increasing with dose; plasma concentrations were consistent with dose proportionality ^1.
Kuhre et al., EBioMedicine (2025)
Preclinical pharmacology
Model: Cells, mice and rats
In obese rats, 21 days of amycretin reduced energy intake by 47% and body weight by 18% versus vehicle while maintaining energy expenditure ^5.

Doses used in published trials

What investigators administered in the cited studies, recorded as a fact about those studies. Not a protocol and not a recommendation.

Full dosing reference, study durations and vial arithmetic →

In the subcutaneous phase 1b/2a study (NCT06064006), once-weekly amycretin was escalated from 0.3 mg to 60 mg over 36 weeks in Part B, and from 0.3 mg to maintenance doses of 20 mg (36 weeks), 5 mg (28 weeks) or 1.25 mg (20 weeks) in Parts C to E ^2.
In the subcutaneous phase 2 trial in type 2 diabetes (NCT06542874), participants were randomized 6:1 to once-weekly amycretin or placebo and then to maintenance doses of 0.4, 1.5, 5, 10, 20 or 40 mg, starting at 0.2 mg with escalation every 4 weeks ^3.
In the oral phase 2 trial in type 2 diabetes, participants were randomized 5:1 to once-daily oral amycretin or placebo with maintenance doses of 6, 25 or 50 mg, starting at 1.5 mg with escalation every 4 weeks ^4.
In the oral first-in-human study (NCT05369390), single doses of 1 to 25 mg, 10-day multiple doses of 3 to 12 mg once daily, and 12-week fixed titration regimens up to two 50 mg tablets in a single daily dose were tested ^1.
In a single-dose renal impairment study (NCT06559527), 42 adults (14 with normal renal function and 7 per renal impairment group, including end-stage renal disease) received one subcutaneous 0.3 mg dose with 4 weeks of follow-up ^11.
The subcutaneous phase 2 trial in type 2 diabetes randomized 262 participants: 38 to 0.4 mg, 36 to 1.5 mg, 37 to 5 mg, 38 to 10 mg, 38 to 20 mg, 38 to 40 mg and 37 to placebo ^3.
The oral phase 2 trial in type 2 diabetes randomized 186 participants: 54 to 6 mg, 51 to 25 mg, 51 to 50 mg and 30 to placebo ^4.
In the subcutaneous phase 1b/2a study, 125 participants were randomized (101 to amycretin, 24 to placebo); Parts C to E sustained the maintenance dose for the last 12 weeks ^2.
In the oral first-in-human study, 144 participants were enrolled (48 in Part A, 36 in Part B, 60 in Part C/D); the Part C/D fixed-titration groups went from 3 mg to 50 mg, from 6 mg to 2 × 50 mg, and from 3 mg to 2 × 25 mg once daily ^1.
Phase 3 registrations under the name zenagamtide include AMAZE 7 (NCT07668414; once-weekly subcutaneous zenagamtide versus two semaglutide doses, primary endpoint at week 84, estimated 650), AMAZE 9 (NCT07720271; one of 5 oral once-daily dose levels versus placebo, week 76, estimated 950), AMBITION 7 (NCT07797335; once-weekly subcutaneous versus insulin glargine in type 2 diabetes, week 52, estimated 1,778) and AMBIENCE (NCT07861100; once-weekly subcutaneous with dose escalation versus placebo in atherosclerotic cardiovascular disease, estimated 8,500); dose amounts are not stated in the registry fields ^6,12,13,7.

Amycretin draw calculator

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Water	mg/mL	Draw
0.5 mL	20	—
1 mL	10	—
1.5 mL	6.667	—
2 mL	5	—
2.5 mL	4	—
3 mL	3.333	—
5 mL	2	—

Published adverse-event data

Reported in the cited trials or product labels. Frequencies apply to the stated population and do not transfer to other settings.

Treatment-emergent adverse events (any)
89 of 144 participants (62%); gastrointestinal events made up 180 of 364 events (49%)
Oral first-in-human phase 1 ¹ · All mild or moderate; no deaths
Gastrointestinal adverse events
Most common event type (rates per group not given in the abstract)
Subcutaneous phase 1b/2a, overweight or obesity ² · Mostly mild to moderate and resolved by end of study
Serious adverse events
21 of 261 participants (8%) overall, including 3 in the placebo group
Subcutaneous phase 2, type 2 diabetes ³ · Serious; no deaths
Gastrointestinal adverse events
26% (6 mg), 41% (25 mg), 47% (50 mg) versus 23% placebo
Oral phase 2, type 2 diabetes ⁴ · Most common event type
Serious adverse events
7 of 186 participants (4%) receiving oral amycretin; none with placebo
Oral phase 2, type 2 diabetes ⁴ · Serious; no deaths

Emerging safety signals

The subcutaneous phase 1b/2a study reported that a large number of participants withdrew, with a high proportion of discontinuations for reasons unrelated to adverse events; this limits interpretation of the body-weight estimates ^2. ² (2025)
In the oral first-in-human study, adverse events increased in frequency in a dose-dependent manner ^1. ¹ (2025)

What is not known: No regulatory approval exists, so there is no label. A human half-life, long-term outcome data and cardiovascular outcomes were not available in the sources reviewed; a cardiovascular outcomes trial was registered but not yet recruiting ^7. The obesity data come from a single-centre early-phase study with many withdrawals. All human studies were funded by the developer.

Background viewing

We haven't found a clinician video focused on Amycretin yet. Meanwhile, this widely watched talk covers the science of aging in general. It does not discuss Amycretin.

David Sinclair, PhD (Harvard Medical School) on the biology of aging

The Diary Of A CEO · 6.9M views · 2026

These creators are not affiliated with Amiravo and do not endorse Amiravo or any product linked on this site. Nothing here is medical advice. Video views counted on YouTube as of Oct 24, 2026.

Regulatory status

Status: Investigational. The 2026 phase 2 reports describe zenagamtide (formerly amycretin) as a novel agent ^3,4, phase 3 trials are registered under the zenagamtide name ^6,7, and an openFDA query of Drugs@FDA on 22 October 2026 returned no application record for either name ^8.
United States (FDA): Amycretin (zenagamtide) is investigational; openFDA queries of Drugs@FDA application data on 22 October 2026 returned no application record under either name ^8, and phase 3 trials were registered ^6,7.
Sport (WADA): Amycretin is not named in the 2026 Prohibited List text reviewed. The list's S0 class covers pharmacological substances not addressed elsewhere that have no current approval by any governmental regulatory health authority, including drugs in clinical development; athletes should consult WADA directly ^10.

Status varies by country and changes over time. How we describe regulatory status.

Quality and testing notes

PubChem held a substance record for amycretin but no computed compound record when checked on 22 October 2026 [9]. The developers report a molecular formula of C343H550N94O116 and an average molecular weight of 7847 Da [5], so a certificate of analysis for a research material would be expected to show identity by mass spectrometry against that mass, HPLC purity, endotoxin and net peptide content, and confirmation of the fatty-acid side chain.

How purity testing works · Reading a certificate of analysis

Check a Amycretin certificate of analysis

Storage and handling

Storage conditions for research material are set by the supplier's documentation; lyophilized peptides are generally sensitive to heat, light and moisture.

Frequently asked questions

What is amycretin?

Amycretin is an investigational single peptide that combines a GLP-1 receptor agonist portion and an amylin receptor agonist portion joined by a linker ^5.

Is amycretin the same as zenagamtide?

Yes. 2026 publications describe zenagamtide as the new name for amycretin ^3,4.

Is it FDA-approved?

No. Drugs@FDA queries on 22 October 2026 returned no application record, and phase 3 trials were registered ^8,6,7.

How large were the body-weight changes in early trials?

In a phase 1b/2a subcutaneous study, the highest-dose group had an estimated mean change of -24.3% at week 36 versus -1.1% with placebo; the study was single-centre with many withdrawals ^2.

Is there an oral form?

Yes. Oral once-daily tablets were tested in a phase 1 study and a 36-week phase 2 trial in type 2 diabetes ^1,4.

What adverse events were most common?

Gastrointestinal events, which became more frequent at higher doses ^1,4.

Latest indexed research

A Research Study to Look at How Well Zenagamtide Works Compared to Placebo in People With Established Atherosclerotic Cardiovascular Disease and Either Overweight or Obesity
Registered trial · humans · Novo Nordisk A/S · 2026-10-06
A Research Study Investigating How Adults With Overweight or Obesity, With or Without Type 2 Diabetes, Tolerate Switching to a New Treatment (Zenagamtide) From Their Current Semaglutide Medication
Registered trial · humans · Novo Nordisk A/S · 2026-10-02

Search all studies on Amycretin (PubMed, Europe PMC, ClinicalTrials.gov)

Listed by publication type from the index record. Inclusion is not an endorsement; open the source to read the findings.

Revision history

Meaningful changes to this entry, with dates and sources. Last reviewed Oct 23, 2026. Typo and layout fixes are not listed.

New section· Schedules by time periodOct 23, 2026
Added week-by-week schedules from registered trials (3 groups, 13 arms).
Source: Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study

References

Last reviewed October 23, 2026 by the Amiravo editorial team.

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Specifications

Format: Lyophilized vial
Type: Single compound

Chemical identifiers are shown only when verified against PubChem.

Research stats

How much has been published, not how good it is.

PubMed records: 28
Indexed as human research: 18
Animal-only research: 0
Randomized controlled trials: 4
Registered trials: 9
Trials with posted results: 0

PubMed records per year (current year is partial).

Counts from title/abstract searches of PubMed, ClinicalTrials.gov, openFDA and NIH RePORTER, checked 2026-10-24. Names shared with other substances can inflate counts. FAERS reports are spontaneous and do not establish cause. Funding shows interest, not evidence. Method

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