The combination of cagrilintide (an amylin analog) with semaglutide (a GLP-1 receptor agonist) — known as CagriSema — represents the next generation of weight management pharmacotherapy. Phase III trials have demonstrated weight loss of 22-25% over 68 weeks — significantly exceeding the 15-17% achieved by semaglutide alone and approaching the results of bariatric surgery.
Amylin: The Complementary Satiety Hormone
Amylin is co-secreted with insulin from pancreatic beta cells in response to meals. It acts on the area postrema and nucleus tractus solitarius in the brainstem to reduce food intake, slow gastric emptying, and suppress glucagon. Critically, amylin and GLP-1 act on different receptors in different brain regions — their combination produces additive rather than redundant appetite suppression.
SURPASS-CVOT and Phase III Data
The REDEFINE 1 trial (n=3417) demonstrated 22.7% mean weight loss with CagriSema 2.4mg/2.4mg vs 8.2% with placebo at 68 weeks. Importantly, 40.4% of participants achieved ≥25% weight loss — a threshold previously achievable only with surgical intervention. The combination also produced greater improvements in cardiometabolic risk factors (HbA1c, blood pressure, lipids) than either compound alone.
Current Availability
Cagrilintide is not yet commercially available as a standalone compound — it is currently in Phase III trials as part of the CagriSema combination. Physician-supervised compounding pharmacies may have access to investigational protocols. Semaglutide alone remains the most evidence-based option for physician-supervised weight management.