TL;DR: Zenagamtide is the new name for amycretin, Novo Nordisk’s investigational peptide that activates both the GLP-1 receptor and the amylin receptor from a single 68-amino-acid chain — not two drugs sharing a vial, but one molecule doing both jobs. At ADA 2026, the 40 mg dose produced up to 14.6% mean weight loss and an A1C reduction of up to 1.71 percentage points over 36 weeks in adults with type 2 diabetes, with most side effects being mild-to-moderate nausea. It is phase 2, unapproved, and being developed in both oral and subcutaneous forms.
What is zenagamtide?
Zenagamtide (development code NNC 04870111, formerly known by its research name amycretin) is an investigational peptide from Novo Nordisk that activates two separate hormone receptor systems — GLP-1 and amylin — from within a single molecule. Novo Nordisk renamed amycretin to zenagamtide as the compound moved through its phase 2 program, and both names refer to the same molecule; older papers, preprints, and the Lancet phase 1b/2a publication still use “amycretin.”
Structurally, zenagamtide is a 68-amino-acid unimolecular peptide: a calcitonin-based amylin receptor agonist sequence joined by a short glycine/glutamic-acid linker to a GLP-1 receptor agonist sequence related to semaglutide. The GLP-1 half carries a C18 diacid side chain for reversible albumin binding — the same fatty-acid trick that gives semaglutide and cagrilintide their long half-lives — and an unnatural amino acid (2-aminoisobutyric acid) that resists DPP-4 breakdown. The result is one continuous peptide chain capable of engaging both the GLP-1 receptor and the amylin receptor (AMYR) in target tissue.
One molecule, not two drugs
This is the detail most coverage glosses over, and it is the whole point of zenagamtide. Compare it with CagriSema, Novo Nordisk’s other dual-pathway candidate: CagriSema is a fixed-dose co-formulation of two separate, independently manufactured peptides — cagrilintide and semaglutide — mixed into one weekly injection. Each component has its own synthesis, its own individual pharmacokinetics, and (as detailed in our cagrilintide overview) its own standalone research literature.
Zenagamtide skips the mixing step entirely. It is synthesized as one continuous peptide chain with both receptor-binding pharmacophores built into the same backbone, connected by a linker rather than co-packaged in the same vial. That distinction matters for a few practical reasons: a unimolecular design has a single pharmacokinetic profile rather than two overlapping ones, a single manufacturing process rather than two, and — at least in principle — more predictable dose-ratio behavior, since the GLP-1 and amylin activity can’t drift apart the way two co-administered molecules theoretically could.
The ADA 2026 type 2 diabetes data
The headline dataset so far comes from a 36-week, randomized, double-blind, placebo-controlled phase 2 dose-finding trial in 262 adults with type 2 diabetes whose A1C was inadequately controlled (7.0–10.0%) on metformin, with or without an SGLT2 inhibitor. Participants were randomized to one of six once-weekly subcutaneous zenagamtide doses (0.4 mg to 40 mg) or placebo. Novo Nordisk presented the results at the American Diabetes Association’s 2026 Scientific Sessions.
At the top 40 mg dose, mean weight loss reached 14.6% versus 2.1% on placebo, with no sign of a weight-loss plateau at the highest doses tested. From a mean baseline A1C of 7.8%, the 40 mg group saw a reduction of up to 1.71 percentage points, versus roughly 0.14 points on placebo — a treatment difference of about 1.56 points. Novo Nordisk also reported that up to 89.1% of participants on zenagamtide reached an A1C below 7%, and 76.2% reached 6.5% or below.
Phase 2, randomized, placebo-controlled, N=262 adults with T2D on metformin ± SGLT2i.
Baseline A1C ~7.8%. Reported treatment difference vs placebo at 40 mg: ~1.56 percentage points.
Adverse events followed the pattern familiar from every incretin and amylin compound in this class: gastrointestinal, mostly nausea, and predominantly mild to moderate in severity.
Why 14.6% is a bigger deal than it looks
It’s tempting to compare 14.6% directly against headline obesity-trial numbers and shrug — but that comparison mixes two different populations, and the mismatch is the most important nuance in the whole zenagamtide story.
The 14.6% figure comes from adults with type 2 diabetes, a population that consistently shows smaller weight-loss responses to incretin therapy than people without diabetes, on every GLP-1 and amylin drug studied so far (semaglutide, tirzepatide, and cagrilintide/semaglutide combinations all show the same gap between their diabetes and non-diabetes trial arms). Zenagamtide’s own earlier data illustrates the gap directly: in a separate phase 1b/2a trial in adults with overweight or obesity but without diabetes, a 20 mg subcutaneous dose produced 22.0% weight loss versus 1.9% on placebo at 36 weeks — using a lower dose than the 40 mg tested in the diabetes trial. Set the two programs side by side and 14.6% in a harder-to-treat population, at a dose ceiling that hadn’t yet plateaued, reads as a stronger signal than the raw number suggests on its own.
How the two zenagamtide programs have progressed
Novo Nordisk has been running zenagamtide (as amycretin) through parallel programs — one in obesity/overweight, one in type 2 diabetes — plus early oral-formulation work using SNAC as a permeation enhancer, the same absorption-boosting approach used in oral semaglutide.
- 1
Early 2024 — Phase 1, oral
First-in-human data for the oral formulation, using an SNAC-based permeation enhancer.
- 2
2025 — Phase 1b/2a, subcutaneous, obesity/overweight
Published in The Lancet: up to 22.0% weight loss at the 20 mg dose (36 weeks, no diabetes), prompting Novo Nordisk to advance the obesity program toward phase 3.
- 3
ADA 2026 — Phase 2, subcutaneous, type 2 diabetes
Up to 14.6% weight loss and a 1.71-point A1C reduction at 40 mg over 36 weeks in 262 adults with T2D.
- 4
H2 2026 — Phase 3 planned, type 2 diabetes
Novo Nordisk has stated it plans to initiate a phase 3 program in adults with T2D based on the ADA 2026 readout.
Both programs remain phase 2 or earlier as of this writing. No zenagamtide formulation — oral or subcutaneous — is approved anywhere, and a phase 3 program in type 2 diabetes has only been announced, not yet started.
Zenagamtide vs the rest of the amylin/GLP-1 field
Zenagamtide is one of several attempts to layer amylin signaling onto GLP-1 pathways, alongside CagriSema and amylin-selective candidates like petrelintide. Where CagriSema pairs two full molecules and petrelintide focuses on amylin-receptor selectivity alone, zenagamtide is the field’s most literal test of what a single engineered chain can do across two receptor systems at once. For the broader mechanistic backdrop on amylin biology itself, see our amylin analogs explained guide, and for where all of these candidates sit relative to one another on the pipeline timeline, our next-gen weight loss peptides for 2026 overview tracks the field as a whole.
| Compound | Design | Population (headline figure) | Weight loss (36-68 wk) | Furthest stage |
|---|---|---|---|---|
| Zenagamtide | Unimolecular GLP-1 + amylin | Type 2 diabetes | Up to 14.6% (36 wk, 40 mg) | Phase 2 |
| Zenagamtide | Unimolecular GLP-1 + amylin | Obesity, no diabetes | Up to 22.0% (36 wk, 20 mg) | Phase 1b/2a |
| CagriSema | Co-formulated cagrilintide + semaglutide | Obesity, no diabetes | ~22.7% (68 wk) | Phase 3 |
| Semaglutide | GLP-1 monotherapy | Obesity, no diabetes | ~15-17% (68 wk) | Approved |
Reading this table by row matters more than reading it by column: the population and trial duration behind each number are doing as much work as the drug itself.
What’s still unverified
A handful of numbers circulating around zenagamtide deserve a caveat rather than a flat citation. The 89.1% figure for participants reaching an A1C below 7% and the companion 76.2% figure for 6.5% or below both trace back to Novo Nordisk’s own ADA 2026 announcement rather than an independent peer-reviewed publication yet, so treat them as company-reported until a journal writeup appears. The amino-acid count (68) and the linker chemistry are documented in secondary summaries of the Lancet phase 1b/2a paper rather than something Novo Nordisk restates in every press release, so it’s worth checking the primary Lancet text directly if you need it for a citation. Nothing here is speculative, but the tier of source varies by claim, and it’s worth keeping that tier in mind before repeating any single number as settled science.
Frequently asked questions
Is zenagamtide the same thing as amycretin?
Yes. Zenagamtide is the name Novo Nordisk assigned to the molecule previously known as amycretin (development code NNC 04870111) as it progressed through its clinical program. Older publications, including the 2025 Lancet phase 1b/2a paper, still refer to it as amycretin.
Is zenagamtide two drugs combined, like CagriSema?
No, and this is the core distinction. CagriSema is a fixed-dose co-formulation of two separate molecules, cagrilintide and semaglutide, mixed into one injection. Zenagamtide is a single 68-amino-acid peptide chain engineered to activate both the GLP-1 receptor and the amylin receptor itself, with no second molecule involved.
How much weight loss has zenagamtide shown in trials?
It depends on the population. In adults with type 2 diabetes, the 40 mg dose produced up to 14.6% mean weight loss over 36 weeks at ADA 2026. In a separate, earlier trial in adults with overweight or obesity but no diabetes, a 20 mg dose produced up to 22.0% weight loss over the same 36-week window — a reminder that diabetes and non-diabetes populations aren’t directly comparable.
Is zenagamtide available or approved?
No. Zenagamtide has only completed phase 2 testing in type 2 diabetes and phase 1b/2a testing in obesity. It is not approved for any use in any jurisdiction, and Novo Nordisk has only announced plans, not a start date beyond H2 2026, for a phase 3 type 2 diabetes program.
Will zenagamtide come as a pill or an injection?
Potentially both. Novo Nordisk has run parallel programs for an oral formulation (using an SNAC-based permeation enhancer, the same approach behind oral semaglutide) and a once-weekly subcutaneous injection. Both routes remain in active development.
What side effects showed up in the trials?
The adverse events reported at ADA 2026 were predominantly gastrointestinal, mostly nausea, and the majority were described as mild to moderate in severity — consistent with the tolerability profile seen across GLP-1 and amylin-based compounds generally.
References
- Novo Nordisk. “Novo Nordisk’s investigational zenagamtide shows significant A1C reductions with up to 14.6% weight loss in adults with type 2 diabetes — presented at ADA 2026.” PRNewswire, 2026.
- Novo Nordisk. “Novo Nordisk advances cardiometabolic pipeline with new data featuring CagriSema and zenagamtide at the American Diabetes Association’s 2026 Scientific Sessions.” PRNewswire, 2026.
- “Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.” The Lancet. 2025.
- Novo Nordisk. “Novo Nordisk advances early-stage obesity medication, amycretin, to phase 3 clinical development based on early-phase clinical trial results in people with obesity or excess weight, published in The Lancet.” PRNewswire, 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.” The Lancet. 2025.
Last updated: June 26, 2026
Disclaimer: This information is for educational and research purposes only.