Articles / Mechanism
Amylin: the second hormone behind the next wave of obesity drugs
After GLP-1, most of the large obesity developers have an amylin programme. What the hormone does, how the leading assets compare and where the evidence is still thin.
Published Oct 10, 2026 ยท 7 min read
Nearly every approved obesity drug is built on GLP-1. The next platform is amylin, and most of the large developers now have an asset in the clinic. The first amylin-based obesity product, CagriSema, has an FDA decision expected in Q4 2026.
Mechanism
Amylin is co-secreted with insulin by pancreatic beta cells after a meal. It signals satiety to the brain, slows gastric emptying and suppresses post-meal glucagon. It acts on the brainstem through a pathway distinct from GLP-1, which is the rationale for both combinations (additive effect) and monotherapy (a potentially gentler gastrointestinal profile).
The concept is not new: pramlintide (Symlin) has been approved for diabetes since 2005 but requires injections before every meal. The current wave rests on long-acting analogues that allow weekly dosing.
The leading assets
| Asset | Company | Design | Best weight loss | Stage |
|---|---|---|---|---|
| CagriSema | Novo Nordisk | Cagrilintide + semaglutide | 22.7%, 68 wk | FDA decision Q4 2026 |
| Eloralintide | Eli Lilly | Amylin agonist | 20.1%, 48 wk | Phase 3 |
| Amycretin | Novo Nordisk | Amylin/GLP-1 in one molecule | ~22%, 36 wk | Phase 3 |
| Petrelintide | Zealand / Roche | Amylin agonist | 10.7%, 42 wk | Phase 3 starting |
Only CagriSema has completed Phase 3. Phase 2 and earlier results tend to shrink in larger trials.
CagriSema
REDEFINE 1 showed 22.7% weight loss at 68 weeks (efficacy estimand), more than semaglutide alone, but the head-to-head REDEFINE 4 trial against tirzepatide missed its non-inferiority goal. Nausea was high at 55.0%; discontinuation for adverse events was 6.0%. It scores 5.2 on our GLP-1 Performance Index.
Petrelintide
The tolerability case for amylin monotherapy. ZUPREME-1 (published September 2026) reported up to 10.7% weight loss at 42 weeks with nausea in 20% (6% on placebo) and about 1% discontinuing for gastrointestinal events. The efficacy is roughly half that of the leading incretins.
Eloralintide
Lilly's monotherapy reached 20.1% at 48 weeks in Phase 2, competitive with GLP-1 drugs on its own. Combined with tirzepatide in people with type 2 diabetes it reached 23.3% vs 14.8% for tirzepatide alone, but with markedly higher discontinuation. A combined product enters Phase 3 by the end of 2026.
Amycretin
A single molecule active at both receptors. Early data showed about 22% at 36 weeks with no plateau, but gastrointestinal events were reported by 94% at the higher doses.
What to watch
The CagriSema decision, whether amylin monotherapy's tolerability advantage holds in Phase 3, and whether amylin preserves lean mass better than incretins, a claim that is not yet supported by robust data. Track timing in the pipeline calendar.