Zenagamtide (amycretin): the phase 2 papers and the AMAZE phase 3 trials
Prepared by: Research Desk. Sources are linked for verification.
Published 28 October 2026
At a glance
- What it is: zenagamtide, previously known as amycretin, is an investigational single-molecule peptide from Novo Nordisk that acts on both GLP-1 and amylin receptors
- New name: the 2026 phase 2 papers call it "zenagamtide (formerly amycretin)", and newer trial registrations use the new name
- Peer-reviewed data: two early-phase papers in The Lancet in July 2025 and two phase 2 papers in people with type 2 diabetes in The Lancet in August 2026
- Phase 3: the AMAZE programme lists at least eleven registered trials, plus separate diabetes, cardiovascular and heart failure trials
- Status: zenagamtide is not approved anywhere; every result below comes from clinical trials
One molecule, two receptor families
Most incretin-based drugs act on the GLP-1 receptor, sometimes combined with GIP or glucagon receptors. Amylin is a different pancreatic hormone, released with insulin, whose receptors are complexes of the calcitonin receptor with receptor activity-modifying proteins. Novo Nordisk's earlier approach, CagriSema, pairs two separate molecules. Zenagamtide puts GLP-1 and amylin receptor activity into a single peptide, and the 2026 papers describe it as an agonist of GLP-1, amylin and calcitonin receptors.
A study in mice and rats by Novo Nordisk scientists (Kuhre et al., 2025) reported that the molecule activated human, mouse and rat GLP-1, amylin and calcitonin receptors in cell-based systems, and lowered food intake and body weight in diet-induced obese rats over 21 days.
The 2025 early-phase papers
Two papers appeared together in The Lancet on 12 July 2025.
- Oral form, phase 1 (Gasiorek et al., 2025, NCT05369390): a first-in-human, placebo-controlled study of 144 adults with overweight or obesity at one research unit in San Antonio, Texas, from May 2022 to January 2024. There were 364 adverse events in 89 of the 144 participants, all mild or moderate, and about half were gastrointestinal. No deaths occurred.
- Injectable form, phase 1b/2a (Dahl et al., 2025, NCT06064006): 125 adults were randomly assigned to zenagamtide (101) or placebo (24) between September 2023 and April 2024. Across four parts with different maintenance strengths and lengths, mean weight change ranged from −9.7% at 20 weeks to −24.3% at 36 weeks with zenagamtide, against −1.1% to +2.3% with placebo.
Both studies were small, short and funded by Novo Nordisk, with company staff among the authors. Their main purpose was to measure safety and how the body handles the molecule, not to establish efficacy.
The 2026 phase 2 papers in type 2 diabetes
On 30 July 2026 The Lancet published two papers from a phase 2 programme registered as NCT06542874, run at 83 sites in 11 countries. Adults with type 2 diabetes on metformin, with or without an SGLT2 inhibitor, took part for 36 weeks. Enrolment ran from August to December 2024.
- Injectable arm (Mora et al., 2026a): 262 participants were randomised, 225 to six zenagamtide strengths and 37 to placebo. From a mean baseline glycated haemoglobin (HbA1c) of 7.8%, the estimated change at week 36 ranged from −0.9 to −1.7 percentage points with zenagamtide. Serious adverse events were reported in 21 of 261 participants exposed, three of them on placebo, and no deaths occurred.
- Oral arm (Mora et al., 2026b): 186 participants were randomised to three zenagamtide strengths or placebo. HbA1c fell by an estimated 0.9 to 1.4 percentage points with zenagamtide. Gastrointestinal adverse events were reported in 26% to 47% of participants in the zenagamtide arms and 23% with placebo. A correction to this paper was published on 24 October 2026.
- Body weight: in Novo Nordisk's June 2026 announcement of the injectable results, mean weight change at week 36 was up to −14.6% with zenagamtide, against −2.1% with placebo.
Weight change was a secondary measure in this trial, and the injectable figure comes from the company's release and a meeting poster rather than from the paper's abstract.
The phase 3 programme on ClinicalTrials.gov
The registry lists the following phase 3 trials (records checked 28 October 2026).
- AMAZE 1 (NCT07339423): excess body weight, about 1,150 participants, recruiting since February 2026
- AMAZE 2 (NCT07533175): excess body weight with type 2 diabetes, about 630 participants
- AMAZE 3 and AMAZE 4 (NCT07571005, NCT07571109): excess body weight with obstructive sleep apnoea, without and with positive airway pressure, about 300 participants each
- AMAZE 5 and AMAZE 6 (NCT07481630, NCT07509307): excess body weight with knee osteoarthritis, about 400 participants each
- AMAZE 7 (NCT07668414): a head-to-head comparison with semaglutide, about 650 participants
- AMAZE 8 (NCT07400107): a comparison with semaglutide in people with type 2 diabetes, about 1,000 participants, not yet recruiting
- AMAZE 9 (NCT07720271): the tablet form, about 950 participants
- AMAZE 10 and AMAZE 13 (NCT07822061, NCT07668401): participants in Japan and in Asia, about 400 each; AMAZE 13 is not yet recruiting
- AMAZE 12 (NCT07503210): maintenance of weight already lost, about 606 participants, active but no longer recruiting
- AMBITION 7 (NCT07797335): type 2 diabetes, compared with insulin glargine, about 1,778 participants
- HF-POLARIS (NCT07567001): heart failure with obesity, about 5,610 participants
- AMBIENCE (NCT07861100): established atherosclerotic cardiovascular disease with overweight or obesity, about 8,500 participants, not yet recruiting
Estimated primary completion dates run from 2028 to 2030. No phase 3 results have been reported.
Unapproved products sold online
A JAMA Medical News article in October 2026 (Rubin, 2026) discusses a growing black market for unapproved retatrutide and zenagamtide and the risks it describes. Material sold under these names outside the trials is not the investigational product tested above, and the trial results say nothing about its identity, purity or contents.
Limitations of the evidence
- Short trials: the published studies ran for 36 weeks at most, and the largest had 262 participants
- Sponsor involvement: every trial is funded by Novo Nordisk, and company employees are among the authors
- Release data: the headline phase 2 weight figure comes from a company announcement and a poster
- Surrogate measures: HbA1c and body weight are not outcome measures such as heart attacks or deaths; the cardiovascular and heart failure trials are still running
- Tolerability: gastrointestinal adverse events were common, as with other GLP-1 and amylin-based molecules
Key terms
- Unimolecular co-agonist: a single molecule designed to activate more than one receptor type
- Amylin receptor: a calcitonin receptor paired with a receptor activity-modifying protein (RAMP)
- HbA1c: glycated haemoglobin, a blood measure that reflects average glucose over roughly three months
- International nonproprietary name (INN): the official generic name, such as zenagamtide, that replaces a code or working name
Supplier
Purita is a store that sells peptides for laboratory research use only. It does not list zenagamtide, which is an investigational pharmaceutical product; the link below goes to the store's homepage.
Affiliate disclosure: this is a paid link. KlowSignal earns a commission if a purchase is made through it, at no extra cost to the buyer. A listing is not an endorsement or a statement about product quality. See the affiliate disclosure.
Related pages
- Research peptide signals: studies and regulatory updates
- About KlowSignal
- How to read a research or regulatory signal
- Eloralintide: the amylin agonist's phase 2 data and phase 3 trials
- CagriSema phase 3: what the REDEFINE trials have reported so far
- Retatrutide phase 3: TRIUMPH-1 and TRIUMPH-2 results published
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