Also known as: AM833 · CagriSema (combined with semaglutide)
Cagrilintide (AM833) is a long-acting amylin analogue developed by Novo Nordisk. It mimics the satiety and gastric-emptying effects of endogenous amylin through calcitonin receptor activation. In combination with semaglutide as CagriSema, Phase 3 data showed up to 22.7% weight loss — approaching efficacy seen with triple agonists.
Amylin is a peptide hormone co-secreted with insulin from pancreatic beta cells in response to meals. It plays a critical role in post-prandial glucose regulation by slowing gastric emptying, suppressing post-meal glucagon, and signaling satiety through brainstem receptors.
Cagrilintide (AM833) is a fatty acid-modified amylin analogue engineered for once-weekly dosing. As a monotherapy, cagrilintide achieved 10.8% weight loss over 26 weeks in Phase 2 trials. Its combination with semaglutide (CagriSema) achieved 22.7% weight loss at 68 weeks in REDEFINE-1 Phase 3 trial (2024).
Cagrilintide activates amylin receptors (CALCR + RAMP1/2/3 complexes) in the area postrema and nucleus tractus solitarius — regions outside the blood-brain barrier. Receptor activation suppresses food intake, reduces meal size, and prolongs inter-meal intervals.
Like native amylin, cagrilintide slows gastric emptying in a meal-dependent fashion, attenuating post-prandial glucose excursions and prolonging fullness — mechanistically distinct from GLP-1 effects.
Amylin receptor activation suppresses post-prandial glucagon release from alpha cells, reducing hepatic glucose output in the post-meal state.
Cagrilintide adds an amylin-pathway satiety mechanism on top of GLP-1 agonism (when used as CagriSema). Phase 3 REDEFINE-1 showed 22.7% weight loss — approaching retatrutide levels. Side effects are predominantly GI (nausea, vomiting) during escalation, consistent with amylin and GLP-1 class effects. Not currently commercially available as monotherapy; awaiting NDA submission expected ~2025.
As a component of CagriSema, cagrilintide shares the chronic-use model of GLP-1 agonists. The amylin pathway provides complementary satiety signaling that may produce more durable appetite regulation than GLP-1 alone, but discontinuation data from Phase 3 are not yet publicly available. Like semaglutide, long-term use is the intended clinical model.
Class warnings apply from the semaglutide component when used as CagriSema. Avoid in MTC/MEN2 history. Pancreatitis risk. Not approved for use in pregnancy.
Phase 2 monotherapy: 10.8% weight loss at 4.5 mg/week over 26 weeks. Phase 3 REDEFINE-1 (CagriSema 2.4/2.4 mg): 22.7% weight loss at 68 weeks vs. 16.1% for semaglutide alone. NDA submission anticipated 2025.
Ask anything about Cagrilintide — mechanisms, dosing protocols, interactions, or research comparisons.
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