As the race for next-generation obesity and metabolic treatments intensifies, Eli Lilly’s triple agonist retatrutide (targeting GLP-1, GIP, and glucagon receptors) has dominated headlines. However, Novo Nordisk—the pharmaceutical leader behind Ozempic and Wegovy—is advancing its own dual-action contender: zenagamtide (formerly known in early clinical trials as amycretin).

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A Different Mechanism: GLP-1 + Amylin Dual Agonism

Rather than following a triple-agonist strategy, Novo Nordisk designed zenagamtide as a single peptide molecule engineered to co-activate two distinct metabolic pathways:

• • GLP-1 (Glucagon-Like Peptide-1): Slows gastric emptying, enhances feelings of fullness, and reduces appetite signaling in the brain.

• • Amylin: A neuroendocrine hormone co-secreted with insulin that regulates post-meal glucose spikes and reinforces appetite suppression.

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Phase 2 Clinical Data: Efficacy Without a Plateau

In Phase 2 clinical trials evaluating injectable zenagamtide, the drug demonstrated noteworthy weight reduction milestones across two primary cohorts:

• • General Obesity Cohort: Achieved an average weight reduction of 24.3% at the highest dose (60 mg) over 36 weeks (~8 months). Novo Nordisk reported no apparent weight-loss plateau at week 36, indicating sustained ongoing weight reduction.

• • Type 2 Diabetes Cohort: Achieved an average weight loss of approximately 14.6% at 36 weeks at the top dose, reflecting the expected metabolic variation seen between non-diabetic and diabetic patient populations.

 

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Profile Comparison & Clinical Considerations

Factor	Clinical Profile
Target Pathways	Dual agonist (GLP-1 receptor + Amylin receptor)
Formulations	In development as both once-weekly subcutaneous injections and oral formulations
Tolerability Profile	Primarily mild-to-moderate GI adverse events (nausea, vomiting, diarrhea)
Comparative Data	No head-to-head clinical trials conducted against retatrutide to date

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Looking Ahead: The Phase 3 Amaze Program

Novo Nordisk is advancing zenagamtide into its Phase 3 Amaze clinical program. Among the upcoming studies, Amaze 8 is designed to test once-weekly zenagamtide in a direct head-to-head comparison against semaglutide in patients with excess weight and Type 2 diabetes. While top-line efficacy percentages will drive early comparisons, the market winner in next-generation metabolic care will ultimately be determined by a balance of real-world tolerability, dosing convenience, patient adherence, and lean muscle preservation.