Amycretin
Medium EvidenceA unimolecular GLP-1 and amylin receptor dual agonist in Phase 3 trials, available in both subcutaneous and oral formulations, with up to 22% weight loss in Phase 1b/2a.
What It Is
Amycretin (now officially named zenagamtide by Novo Nordisk, NNC9204-1177) is a first-in-class unimolecular agonist that simultaneously activates both the glucagon-like peptide-1 (GLP-1) and amylin receptors, developed by Novo Nordisk. Unlike combination therapies, amycretin integrates both mechanisms into a single molecule and is being developed in both subcutaneous and oral formulations. Phase 2 data in type 2 diabetes (n=448, 36 weeks) showed significant results: subcutaneous amycretin achieved up to 14.5% weight loss with HbA1c reductions up to 1.5% (77.6% of participants reaching HbA1c <7%), while the oral formulation achieved dose-dependent weight loss up to 10.1% with HbA1c improvements up to 1.5%. In the Phase 1b/2a obesity trial (published in The Lancet 2025), subcutaneous amycretin achieved approximately 22% weight loss at 36 weeks with no plateau observed. In May 2026, Novo Nordisk expanded the pivotal amycretin program, planning Phase 3 development for type 2 diabetes in addition to the obesity Phase 3 REDEFINE programme that began enrolling in Q1 2026. An FDA filing is expected in late 2026 or early 2027, with a regulatory decision window opening in 2027–2028. The oral formulation is particularly significant, as it could provide dual-agonist efficacy without injections — a major convenience advantage in the competitive obesity market. At the ADA 2026 Scientific Sessions (June 7, New Orleans), Novo Nordisk presented full Phase 2 dose-finding data for zenagamtide in type 2 diabetes — the first randomized controlled evidence of the compound's glycemic efficacy. The 36-week trial randomized 262 adults with type 2 diabetes inadequately controlled on metformin (±SGLT2 inhibitor, A1C 7.0–10.0%) to six doses of subcutaneous zenagamtide (0.4–40 mg once-weekly) or placebo. The 40 mg dose achieved 14.6% mean weight loss and a 1.71 percentage-point reduction in HbA1c — with 89% of participants at the 40 mg dose reaching the ADA's general A1C target of below 7%, and 77.8% achieving ≤6.5%. All doses met the primary endpoint of A1C reduction; weight reduction endpoints were met at doses ≥1.5 mg. Novo Nordisk confirmed plans to initiate a Phase 3 development program for zenagamtide in type 2 diabetes in H2 2026, in addition to the obesity Phase 3 REDEFINE programme already enrolling. The ADA 2026 T2D data establish zenagamtide as the only unimolecular GLP-1/amylin agonist with Phase 2 evidence across both obesity (22% weight loss, Lancet 2025) and type 2 diabetes populations.
Regulatory Status
Phase 3 REDEFINE programme enrolling for obesity (Q1 2026). Phase 3 for type 2 diabetes initiating H2 2026 (confirmed at ADA 2026, June 7). Phase 2 T2D data (ADA 2026): 14.6% weight loss + HbA1c −1.71% at 40 mg. FDA filing expected late 2026–early 2027.
Effective: Q1 2026
View FDA SourceWhy Researchers Study It
Amycretin is notable as the first unimolecular GLP-1/amylin dual agonist, combining two complementary appetite-suppression pathways in a single molecule. The availability of both injectable and oral formulations provides flexibility. Its 22% weight loss at 36 weeks in early studies rivals the best results from GLP-1-only drugs, and the amylin component may offer unique satiety benefits through hypothalamic and area postrema signaling.
Proposed Mechanisms
- GLP-1 receptor agonism suppresses appetite, slows gastric emptying, and enhances insulin secretion
- Amylin receptor activation promotes satiety through hypothalamus and area postrema signaling
- Dual receptor engagement in a single molecule provides complementary appetite suppression
- Slows gastric emptying through both GLP-1 and amylin pathways
- Improves glycemic control through enhanced insulin sensitivity and secretion
Evidence Snapshot
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| Human (Phase 1b/2a) | Weekly SC amycretin in adults with overweight/obesity, 36 weeks (Lancet 2025) | 22% weight loss with subcutaneous formulation; 13.1% with oral in 12 weeks | Source |
| Human (Phase 2) | SC and oral amycretin in T2D on metformin ± SGLT2i, 36 weeks (n=448) | Up to 14.5% weight loss (SC); HbA1c reduction up to 1.8 pp; 89.1% achieving HbA1c <7% | Source |
| Human (Phase 3) | Obesity/overweight program initiated Q1 2026; T2D program planned | Enrolling; results expected 2028–2029 | Source |
| Human (Phase 2, T2D dose-finding — ADA 2026, June 7) | Adults with T2D on metformin ± SGLT2i (n=262, A1C 7.0–10.0%), 6 doses (0.4–40 mg SC once-weekly) vs placebo, 36 weeks | 40 mg: 14.6% weight loss, HbA1c −1.71%, 89% achieved A1C <7%, 77.8% achieved ≤6.5%; all doses met primary A1C endpoint; weight endpoint met at doses ≥1.5 mg; Phase 3 T2D program planned H2 2026 | Source |
Commonly Discussed Benefits
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Safety & Cautions
- Phase 3 trials have just begun; no pivotal efficacy data yet
- Gastrointestinal side effects (nausea, vomiting) consistent with incretin and amylin class
- Long-term safety and efficacy beyond 36 weeks not yet established
- Oral formulation tolerability at higher doses needs Phase 3 confirmation
- Only available through clinical trial enrollment
Comparisons
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Citations
- [1] Amycretin Phase 1b/2a SC results — The Lancet 2025 PubMed
- [2] Novo Nordisk — Phase 2 T2D trial results, November 2025 PubMed
- [3] Novo Nordisk advances amycretin to Phase III — Clinical Trials Arena 2026 PubMed
- [4] Novo Nordisk expands pivotal amycretin program — Fierce Biotech 2026 PubMed
- [5] Amycretin, a novel unimolecular GLP-1 and amylin receptor agonist: results from a phase 1b/2a RCT — The Lancet 2026 PubMed
- [6] Novo Nordisk — Zenagamtide Phase 2 T2D Data Presented at ADA 2026 (June 7, 2026) PubMed
- [7] Zenagamtide Achieves 89% A1C Target with 14.6% Weight Loss in Diabetes Trial — Clinical Trial Vanguard PubMed
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