Amycretin: Novo's Next-Gen Amylin/GLP-1 Co-Agonist — Phase 2 Data and Pipeline Position

CagriSema combines two separate molecules — semaglutide plus the amylin analog cagrilintide — in a fixed-dose combination injection. Amycretin takes the next step: it puts GLP-1 and amylin receptor agonism into a single molecule. One compound, two receptor targets, one injection (or one pill).

Novo Nordisk announced positive Phase 1b/2a results for subcutaneous amycretin in January 2025, Phase 2 results in type 2 diabetes in November 2025, and received regulatory green light to advance both subcutaneous and oral formulations into Phase 3 in June 2025. Phase 3 trials for obesity were planned to begin in Q1 2026.^1,2,3

The Amylin Mechanism

Amylin is a hormone co-secreted with insulin from pancreatic beta cells. It slows gastric emptying, suppresses glucagon secretion, and promotes satiety through hypothalamic signaling — complementary to but distinct from GLP-1's mechanism. The theory behind combining amylin with GLP-1 is that two satiety signals hitting different pathways produce greater appetite suppression than either alone.

Pramlintide (Symlin), an approved amylin analog for diabetes, never gained traction as a weight-loss drug because it required three daily injections and produced modest weight loss. CagriSema solved the injection frequency problem with a long-acting amylin analog (cagrilintide) combined with semaglutide in a once-weekly shot. Amycretin goes further: a single molecule that activates both receptors, eliminating the need for a fixed-dose combination.

Phase 2 Data: Type 2 Diabetes

The Phase 2 trial enrolled 448 adults with T2D inadequately controlled on metformin (± SGLT2 inhibitor). It tested both subcutaneous (once-weekly) and oral (once-daily) formulations against placebo for 36 weeks.²

The most notable finding: no weight loss plateau was observed at 36 weeks for the higher doses of either formulation. This suggests the drug was still producing weight loss at the end of the trial — meaning final efficacy at longer timepoints could be substantially higher.²

Phase 1b/2a Data: Obesity (Without Diabetes)

Earlier subcutaneous data in people with overweight or obesity (without diabetes) showed approximately 13% body weight reduction at 12 weeks at the highest dose tested — an aggressive trajectory that, if maintained, would project to potentially best-in-class weight loss at 52+ weeks. However, 12-week data is early, and projection to longer timepoints carries significant uncertainty.¹

Where Amycretin Fits

The obesity drug pipeline is increasingly crowded. Here's where amycretin sits relative to other candidates:

Amycretin's unimolecular design gives it a potential manufacturing and formulation advantage over CagriSema's two-component combination. And the oral formulation — if Phase 3 confirms the Phase 2 signal — would make amycretin the first oral GLP-1/amylin drug, potentially competing directly with Foundayo but with superior efficacy through the dual mechanism.