Over the past year, searches for cagrilintide have nearly doubled, peaking in mid-September 2026. The trigger was a paper in Nature Metabolism showing that cagrilintide combined with retatrutide produced greater weight loss in obese rats than either drug alone. Note the last two words — in rats.
It is also one half of Novo Nordisk's CagriSema combination, currently under FDA review. That gives cagrilintide a rare advantage for an unapproved peptide: a Phase III programme with thousands of participants, published in the New England Journal of Medicine.
[What it is]
Amylin is a 37-amino-acid peptide co-released with insulin after meals. It slows gastric emptying, suppresses the post-meal glucagon spike, and signals satiety via the area postrema in the brainstem (Hay et al., 2015, PMID 26071095).
The problem with amylin as a drug is the molecule itself: it aggregates into amyloid fibrils. The first fix was pramlintide, approved in 2005, dosed three times daily. Cagrilintide is the second attempt: Novo Nordisk stabilised the sequence and attached a fatty acid chain so the peptide binds albumin (Kruse et al., 2021, PMID 34288673), extending the half-life to 159–195 hours and enabling once-weekly dosing (Enebo et al., 2021, PMID 33894838).
[Published data]
- REDEFINE 1 monotherapy arm: 10.8% weight loss at 26 weeks (4.5 mg, Phase II); 11.5% at 68 weeks (2.4 mg)
- With semaglutide (CagriSema): 20.4% at 68 weeks
- With retatrutide: no human trial exists
[Dosing]
Trials titrated to 2.4 mg weekly. A 4.5 mg dose was tested in Phase II and dropped because of higher nausea rates. Community protocols copy semaglutide's titration schedule (0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg) and come from no cagrilintide trial. Outside clinical trials, no verified protocol exists.
[Safety]
In the Phase II monotherapy trial, 41–63% of participants reported GI adverse events versus 32% on placebo. With semaglutide, that figure is around 80%. The longest exposure data covers 84 weeks and is not yet formally published. Human safety data for the retatrutide combination is zero.
[Legal status, September 2026]
Not approved in any country. CagriSema is under FDA review. Under US federal law, cagrilintide may not be compounded, and the FDA issued warning letters to suppliers in March 2026.