Zenagamtide
Low EvidenceA unimolecular GLP-1 and amylin receptor co-agonist developed by Novo Nordisk, available in both subcutaneous and oral formulations, with Phase 2 data showing up to 24.3% weight loss and Phase 3 AMAZE trials initiated in 2026.
What It Is
Zenagamtide (NN9487) is an investigational once-weekly unimolecular co-agonist of the GLP-1 receptor and amylin receptor, developed by Novo Nordisk. It is distinct from CagriSema — rather than combining two separately developed molecules, zenagamtide is a single engineered peptide designed to activate both GLP-1 and amylin receptor pathways simultaneously, potentially offering improved pharmacokinetic and tolerability properties compared to a fixed-dose combination. GLP-1 receptor activation reduces appetite and slows gastric emptying, while amylin receptor activation in the hypothalamus and hindbrain produces complementary satiety signaling through a separate neural circuit — the same dual-pathway rationale behind CagriSema, now encoded in one molecule. Phase 2 clinical data presented at the ADA 2026 Scientific Sessions (June 5–8, New Orleans) showed that subcutaneous zenagamtide achieved up to 24.3% weight loss in obesity trials and 14.5% weight loss with 1.8% HbA1c reduction in a type 2 diabetes Phase 2 trial at 36 weeks. The oral formulation demonstrated 7.6% placebo-adjusted weight loss in T2D and approximately 13% in obesity Phase 2 data. Both formulations remained on an ascending trajectory without plateau at study end. In early 2026, Novo Nordisk initiated the Phase 3 AMAZE program: AMAZE 1 (obesity, 84 weeks vs placebo) and AMAZE 2 (T2D + obesity, 84 weeks vs placebo), with additional Phase 3 trials planned for obstructive sleep apnea and knee osteoarthritis in H2 2026. Zenagamtide represents Novo Nordisk's next-generation amylin-GLP-1 asset — a conceptually cleaner successor to the CagriSema combination — and, if Phase 3 data confirm the Phase 2 signal, could become the cornerstone of Novo Nordisk's post-Wegovy pipeline.
Regulatory Status
Phase 3 AMAZE 1 (obesity) and AMAZE 2 (T2D + obesity) initiated in early 2026, 84-week trials. Phase 3 for T2D planned H2 2026. Phase 2 data presented at ADA 2026 Scientific Sessions (June 5–8). Not yet filed with any regulatory agency.
Effective: Early 2026
View FDA SourceWhy Researchers Study It
Zenagamtide is studied as a single-molecule GLP-1/amylin co-agonist — a mechanistic refinement on the dual-pathway obesity thesis demonstrated by CagriSema. Its unimolecular design may simplify dosing, improve pharmacokinetics, and reduce combinatorial complexity compared to fixed-dose combinations, while targeting the same two satiety hormone pathways that have produced the highest weight loss in clinical development.
Proposed Mechanisms
- Activates GLP-1 receptors to reduce appetite and slow gastric emptying
- Activates amylin receptors (area postrema, hypothalamus) via a distinct satiety neuronal circuit
- Dual-pathway satiety signaling from a single unimolecular agent
- Available in both subcutaneous injectable and oral formulations
- Long-acting once-weekly pharmacokinetics designed for stable receptor engagement
Evidence Snapshot
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| Phase 2 (Obesity, subcutaneous) | Adults with obesity — once-weekly subcutaneous zenagamtide | Up to 24.3% weight loss; no plateau at study end | Source |
| Phase 2 (T2D, subcutaneous) | Adults with type 2 diabetes — subcutaneous zenagamtide, 36 weeks | 14.5% weight loss; 1.8% HbA1c reduction; 89% of participants reached HbA1c <7% | Source |
| Phase 2 (T2D, oral) | Adults with type 2 diabetes — oral zenagamtide formulation | 7.6% placebo-adjusted weight loss; 78% of participants reached HbA1c <7%; no plateau | Source |
| Phase 2 (Obesity, oral) | Adults with obesity — oral zenagamtide formulation | ~13% weight loss; ascending trajectory without plateau | Source |
Commonly Discussed Benefits
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Safety & Cautions
- Phase 3 trials initiated but no pivotal results available yet
- Long-term safety profile not established beyond 36-week Phase 2 data
- Not filed or approved by any regulatory agency
- Oral formulation efficacy (~13%) below subcutaneous (~24.3%) — typical of oral GLP-1 class
- Head-to-head comparisons with CagriSema, tirzepatide, and retatrutide not yet available
Comparisons
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Related Peptides
Semaglutide
High EvidenceA GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.
Cagrilintide
High EvidenceA long-acting amylin analog studied for appetite regulation; NDA filed for CagriSema (cagrilintide + semaglutide) combination in December 2025, with FDA review expected in 2026.
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.
CagriSema
High EvidenceA fixed-dose combination of cagrilintide (amylin analog) and semaglutide (GLP-1 agonist) studied for enhanced weight loss through dual hormonal pathways.