Novo Nordisk is gaining confidence in its dual GLP-1/amylin agonist pipeline candidate amycretin after the molecule delivered substantial improvements in both glycemic control and body weight in a Phase 2 trial in adults with type 2 diabetes (T2D). The unimolecular agent, designed for both subcutaneous and oral administration, produced dose-dependent reductions in HbA1c of up to −1.8% and weight loss of up to 14.5% at 36 weeks.
The study specifics
The trial enrolled 448 adults inadequately controlled on metformin with or without an SGLT2 inhibitor, reflecting real-world treatment patterns. Participants received one of nine amycretin regimens, including six weekly subcutaneous doses and three daily oral doses. Across both formulations, amycretin outperformed placebo on all primary and key secondary endpoints.
Up to 89% of participants on the highest subcutaneous dose achieved HbA1c <7%, while weight loss showed no plateau at week 36, a feature increasingly seen with emerging multi-agonist therapies. Oral amycretin demonstrated similar patterns, reinforcing Novo Nordisk’s strategy to grow its portfolio of oral incretin-based medicines.
Safety findings were consistent with expectations for incretin-based therapies, with gastrointestinal events the most common adverse effects and generally mild to moderate in severity.
Amycretin as a differentiated dual agonist
Amycretin’s unimolecular design targets GLP-1 and amylin receptors simultaneously, reflecting a broader mechanistic shift toward leveraging complementary hormonal pathways involved in appetite regulation, energy expenditure, and post-prandial glucose control. Preclinical studies suggest that combining amylin-mediated satiety and delayed gastric emptying with incretin-driven insulinotropic effects may deliver additive or synergistic metabolic benefits, particularly in T2D and obesity where multiple metabolic defects coexist. https://app.allsci.com/article/W4366696743
Novo Nordisk’s chief scientific officer Martin Holst Lange said the results “validate the potential best-in-class profile of amycretin”, and confirmed plans to advance the program into Phase 3 for T2D in 2026. The company previously announced plans for Phase 3 development in weight management, positioning amycretin as a core component of its next-generation multi-agonist strategy.
Context in the competitive multi-agonist landscape
Preclinical and early mechanistic studies have long indicated that combining amylin analogues with GLP-1 agonists may yield greater weight loss than monotherapy and could surpass the efficacy ceiling of single-hormone approaches. Dual-agonist strategies may also streamline dosing, improve adherence, and optimize pharmacokinetic alignment compared with administering two separate drugs.
In parallel to amycretin, Novo Nordisk is also developing CagriSema, a fixed-ratio combination of semaglutide with the long-acting amylin analogue cagrilintide, already in Phase 3. Several major companies—including AbbVie, Roche, Pfizer, Eli Lilly, AstraZeneca, and Zealand Pharma—are also pursuing various amylin-based or multi-agonist metabolic programs, reflecting the interest in amylin biology as part of next-generation incretin therapeutics.