Retatrutide vs Zenagamtide (Amycretin): Comparing Triple-Agonist and GLP-1/Amylin Trial Data
TL;DR: Novo's zenagamtide (amycretin) hit 14.6% weight loss in Phase 2b (ADA 2026); retatrutide's Phase 3 already reported 28.3%.
What Is Zenagamtide (Amycretin) and How Does It Differ From Retatrutide?
Zenagamtide is the international non-proprietary name Novo Nordisk has assigned to amycretin, an investigational peptide first disclosed in 2021 and studied since as a unimolecular dual agonist — a single molecule that activates two receptors at once: the GLP-1 receptor and the amylin receptor.[1] That mechanism is distinct from retatrutide, Eli Lilly's triple agonist, which instead pairs GLP-1 with the GIP and glucagon receptors. Amylin is a pancreatic hormone co-secreted with insulin that is thought to act on satiety and gastric-emptying pathways in the brainstem, so a GLP-1/amylin combination represents a mechanistically independent route to the same broad research question — whether combining incretin-adjacent receptor targets improves on single-receptor GLP-1 agonism — that retatrutide, survodutide and other pipeline dual/triple agonists are also testing.[2]
Zenagamtide is being developed in both subcutaneous and oral formulations and has moved through Phase 1, Phase 1b/2a and, most recently, Phase 2b trials. It is not approved anywhere and remains confined to Novo Nordisk's clinical programme, with no relationship to any Velox Peptides product.
What Did Zenagamtide's Phase 1b/2a Obesity Trial Report?
Design: 125 adults with overweight or obesity, without diabetes, were randomised across escalating once-weekly subcutaneous dose cohorts up to 60mg, versus matched placebo, over 36 weeks at a single trial centre. Result at 36 weeks: mean body-weight loss of 22.0% on the 20mg dose and 24.3% on the 60mg dose, versus 1.1% on placebo. Tolerability: the most frequently reported adverse events were mild-to-moderate gastrointestinal symptoms (nausea, vomiting), increasing with dose and resolving by the end of treatment, consistent with the known GLP-1/amylin class profile.[1]
Source: PMID 40550231; The Lancet, 2025
On the strength of this data, Novo Nordisk advanced amycretin's obesity programme into Phase 3 development, following an earlier first-in-human Phase 1 trial that had already established the compound's basic safety and pharmacokinetic profile.[3]
What Did the New Phase 2b Type 2 Diabetes Data Show?
Design: 262 adults with type 2 diabetes inadequately controlled on metformin, with or without an SGLT2 inhibitor, were randomised to one of six once-weekly subcutaneous zenagamtide doses (0.4mg to 40mg) or matched placebo, over 36 weeks. Result at 36 weeks: the 40mg dose produced up to 14.6% mean body-weight loss versus 2.1% on placebo, with an A1C reduction of up to 1.71 percentage points from a 7.8% baseline; 89.1% of participants on the top dose reached an A1C below 7%.[4]
Source: Diabetes. 2026;75(Suppl_1):1730-P; Novo Nordisk press materials, 2026
This is zenagamtide's most advanced published data specifically in a type 2 diabetes population, and Novo Nordisk has said it plans to move the compound into a dedicated Phase 3 programme for type 2 diabetes in the second half of 2026.[4] As of this writing, that Phase 3 diabetes programme has not yet reported results.
How Do Zenagamtide and Retatrutide's Trial Data Compare Side by Side?
| Compound & dose | Trial (phase) | n | Duration | Reported result |
|---|---|---|---|---|
| Zenagamtide 60mg | Obesity study (Phase 1b/2a) | 125 | 36 wks | −24.3% weight vs 1.1% placebo |
| Zenagamtide 40mg | T2D dose-finding (Phase 2b) | 262 | 36 wks | −14.6% weight; A1C −1.71pp |
| Retatrutide 12mg | TRIUMPH-1 obesity (Phase 3) | 2,339 | 80 wks | −28.3% weight (up to −30.3% at 104 wks) |
| Retatrutide (T2D arm) | TRANSCEND-T2D-1 (Phase 3) | 537 | 40 wks | A1C −2.0pp; weight −16.8% |
Figures are as reported in each publication, at different trial phases, populations, doses and durations. This table is for contextual research reference only and is not a head-to-head clinical comparison.
Read plainly, retatrutide's published numbers are larger in both the obesity and diabetes settings. But the comparison is lopsided by design, not necessarily by biology: retatrutide's figures come from completed, regulatory-grade Phase 3 trials enrolling thousands of participants, while zenagamtide's most advanced diabetes data is still Phase 2b, a smaller dose-finding study whose primary purpose is choosing doses to carry into Phase 3 — not to maximise the headline effect size. Early-phase weight-loss and A1C figures often shift, in either direction, once a larger Phase 3 population and longer follow-up are added.
Why Does the Amylin-Receptor Mechanism Matter for Incretin Research?
A mechanistically distinct combination
Retatrutide, survodutide and mazdutide all pair GLP-1 with the glucagon receptor (retatrutide adds GIP too). Zenagamtide instead pairs GLP-1 with the amylin receptor — a pathway acting through separate satiety circuitry in the brainstem rather than through hepatic glucagon signalling, giving researchers a second independent route to test the combination-agonist hypothesis.
Validates cross-programme interest in multi-receptor agonism
Multiple, independently-run pipelines — Lilly's triple agonist, Novo's GLP-1/amylin dual agonist, Boehringer/Zealand's GLP-1/glucagon dual agonist — all reporting substantial weight-loss and glycaemic signals strengthens the broader research case for multi-receptor incretin agonism, regardless of which compound reaches approval first.
Trial phase gap is the key caveat
Zenagamtide is roughly two full trial phases behind retatrutide's most advanced obesity data. Its Phase 2b diabetes and Phase 1b/2a obesity datasets are early signals, not confirmatory evidence, and could shift materially once Phase 3 trials complete.
What's Next in Zenagamtide's Development Timeline?
Novo Nordisk has indicated a Phase 3 type 2 diabetes programme for zenagamtide is planned to begin in the second half of 2026, building on the Phase 2b dose-finding results.[4] The compound's obesity programme is further along, having already advanced to Phase 3 on the strength of the 2025 Phase 1b/2a data, alongside a parallel oral-formulation development track.[3] None of this overlaps with retatrutide's own pending TRIUMPH-2 and TRIUMPH-3 trials, which are separately tracking towards later-2026 readouts in type 2 diabetes and cardiovascular-disease populations respectively.
What Should UK Researchers Take From This?
Zenagamtide (amycretin) is an unapproved, patent-protected Novo Nordisk investigational compound confined to registered clinical trials. It is not available for purchase, compounding, or research use from any lawful source, and Velox Peptides does not supply it. Its published data is presented here purely as third-party scientific context for researchers tracking the wider incretin-receptor field that retatrutide research sits within.
That does not change retatrutide's own regulatory position. It remains an unlicensed investigational medicine, with a Phase 3 NDA filing targeted for Q4 2026 in the US on its obesity indication and no confirmed MHRA timeline. Velox Peptides supplies retatrutide strictly as an HPLC-verified in vitro research reagent, with batch-specific certificates of analysis, and makes no therapeutic or weight-loss claims for it.
Retatrutide is supplied as a research reagent only. It is not a medicine and has not been evaluated by the MHRA or FDA for use in our products. Not for human or veterinary use. Zenagamtide (amycretin) is not a Velox Peptides product and is not available for sale. See our Research Use Policy and MHRA Statement.
References
- Dahl K, Toubro S, Dey S, et al. Amycretin, a Novel, Unimolecular GLP-1 and Amylin Receptor Agonist Administered Subcutaneously: Results from a Phase 1b/2a Randomised Controlled Study. Lancet. 2025. PMID: 40550231. pubmed.ncbi.nlm.nih.gov
- Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019;30:72–130. PMID: 30120083
- 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. Press release, 2025. prnewswire.com
- Mora C, Aroda VR, Asong M, et al. Zenagamtide (amycretin), a novel unimolecular GLP-1 and amylin receptor agonist: phase 2b results in T2D. Diabetes. 2026;75(Suppl_1):1730-P, presented at ADA 2026 Scientific Sessions, 5–8 June 2026. diabetesjournals.org
- Eli Lilly and Company. Lilly's retatrutide achieved topline weight-reduction results in the TRIUMPH-1 Phase 3 obesity trial. Press release, 21 May 2026. PR Newswire
- TRANSCEND-T2D-1 Phase 3 trial of retatrutide in type 2 diabetes (companion to TRIUMPH-1), published 6 June 2026 — reported A1C reductions of up to 2.0 percentage points and average body-weight reduction of 16.8% at 40 weeks. PubMed: retatrutide TRANSCEND-T2D-1
Frequently Asked Questions
What is zenagamtide (amycretin)?
Zenagamtide is the INN for amycretin, a Novo Nordisk investigational peptide that acts as a unimolecular dual agonist at the GLP-1 receptor and the amylin receptor. It is unrelated to retatrutide's GLP-1/GIP/glucagon triple-agonist mechanism and is not approved for human use in any jurisdiction.
What did zenagamtide's Phase 2b trial show?
Presented as poster 1730-P at the ADA 2026 Scientific Sessions (5-8 June 2026, New Orleans), a 36-week Phase 2b dose-finding trial in 262 adults with type 2 diabetes reported up to 14.6% mean body-weight loss and an A1C reduction of up to 1.71 percentage points on the 40mg subcutaneous dose, versus 2.1% weight loss on placebo.
What did zenagamtide's earlier obesity trial show?
A Phase 1b/2a trial in 125 adults with overweight or obesity (Dahl et al., The Lancet, published 12 July 2025) reported mean weight loss of 22.0% at 36 weeks on the 20mg subcutaneous dose and 24.3% on the 60mg dose, versus 1.1% on placebo. Gastrointestinal adverse events were the most common side effect and were dose-dependent.
How does zenagamtide compare with retatrutide's trial data?
Retatrutide's Phase 3 TRIUMPH-1 trial reported 28.3% weight loss at 80 weeks (up to 30.3% at a 104-week extension), and its companion TRANSCEND-T2D-1 trial reported A1C reductions of up to 2.0 percentage points in type 2 diabetes. Zenagamtide's most advanced published diabetes data is still Phase 2b, reporting a smaller 14.6% weight loss and 1.71-point A1C reduction. The two compounds cannot be compared head-to-head because they are at different trial phases, in different-sized studies, using different receptor mechanisms.
Is zenagamtide or amycretin available as a research reagent?
No. Zenagamtide (amycretin) is an unapproved, patent-protected Novo Nordisk investigational compound confined to registered clinical trials. It is not available for purchase, compounding, or research use from any lawful source, and Velox Peptides does not supply it.
Is retatrutide available as a research reagent?
Yes. Velox Peptides supplies retatrutide as an HPLC-verified (≥99% purity) lyophilised research reagent for in vitro laboratory research only. It is not licensed as a medicine, is not evaluated by the MHRA or FDA, and is not intended for human or veterinary use.