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.
Regulatory Status
Phase 3 REDEFINE programme enrolling for obesity (Q1 2026). Phase 3 for type 2 diabetes planned H2 2026. Subcutaneous and oral Phase 2 complete. 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 |
Commonly Discussed Benefits
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
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