Novo Nordisk’s Amycretin Moves to Phase III: What Sets This Obesity Drug Apart?

Novo Nordisk is advancing both subcutaneous and oral versions of its investigational weight-loss drug amycretin into Phase III clinical development, following positive early-stage findings and regulatory feedback.

What Is Amycretin?

Amycretin is an investigational treatment for adults with overweight or obesity. It combines two naturally occurring hormones — GLP-1 and amylin — into a single molecule. As a unimolecular agonist, amycretin activates both receptors: GLP-1 reduces appetite and improves glucose regulation, while amylin, co-released with insulin after meals, helps slow gastric emptying and enhances satiety.

Unlike leading drugs like semaglutide (GLP-1 receptor agonist only) and tirzepatide (dual GIP/GLP-1 receptor co-agonist), amycretin pairs GLP-1 with amylin, mimicking the body’s natural post-meal hormone signals via two distinct pathways. This mechanism may support greater and more sustained weight loss. Amycretin is being developed in injectable and oral forms, offering added dosing flexibility.

Clinical Trial Data Supporting Amycretin’s Advancement

The Phase III progression follows completed early-stage studies and end-of-Phase II regulatory interactions, which supported the safety, efficacy signals and development plan for both the subcutaneous and oral formulations.

In a Phase Ib/IIa trial completed in January 2025, 125 adults with overweight or obesity received once-weekly subcutaneous amycretin for up to 36 weeks. Participants on the highest dose (20 mg) saw a 22% average weight reduction, compared to roughly 2% weight gain in the placebo group. Lower doses led to reductions of 16.2% (5 mg) and 9.7% (1.25 mg).

The treatment was generally well tolerated. The most common adverse events were gastrointestinal in nature, and the vast majority were mild to moderate in severity, consistent with the expected profile of incretin-based therapies.

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A Growing Shift Toward Multi-Hormone Weight-Loss Therapies

Amycretin enters a market of GLP-1 combination strategies.

Metsera’s trial of its investigational amylin analogue, MET‑233i, showed an 8.4% mean placebo-adjusted weight loss after 36 days in around 80 participants with overweight or obesity. Eli Lilly’s eloralintide achieved up to 11.5% weight loss at 12 weeks in a small Phase I study, with results shared ahead of the 2025 American Diabetes Association (ADA) Scientific Sessions.

Another investigational amylin analogue, GUBamy, recently showed a 7.77% weight loss over six weeks at the 2 mg dose in a Phase I study, compared to a 1.99% gain in the placebo group. Now licensed to AbbVie, GUBamy is also being evaluated for future co-formulation with GLP-1-based agents, signaling its potential for use alone or in combination.

While most current therapies focus on GLP-1 or GIP combinations, amycretin is among the first to integrate GLP-1 and amylin activity into a single molecule.

What’s Next for Novo Nordisk?

Novo Nordisk plans to launch its global Phase III program for amycretin in early 2026, focusing on long-term outcomes in adults with overweight or obesity. Study designs have not been disclosed but are expected to assess efficacy, safety and dosing across diverse populations.

Amycretin adds to the company’s expanding obesity pipeline, which includes investigational candidates like CagriSema (semaglutide + cagrilintide), showing 15.7% weight loss in adults with obesity and type 2 diabetes, and a 25 mg oral semaglutide now under FDA review.

Commercially, Novo Nordisk continues to lead in obesity care, with sales up 67% year-over-year in Q1 2025.

A recent partnership with Septerna to develop oral small molecule agonists targeting GLP-1, GIP and glucagon receptors further underscores Novo Nordisk’s strategy to pursue peptide- and small molecule-based innovations across obesity and cardiometabolic diseases.

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