Cagrilintide

What Is Cagrilintide?

Cagrilintide is a long-acting analogue of amylin, the pancreatic hormone co-secreted with insulin after a meal. Native amylin signals satiety by binding amylin receptors in the area postrema of the hindbrain, a region outside the blood-brain barrier that gates satiety and nausea signals. Cagrilintide reproduces this activity with two engineering changes: it is non-fibrillating, unlike native amylin (which aggregates and is the reason pramlintide required multiple daily injections), and it is albumin-bound, giving a half-life of roughly 7 to 8 days.

It activates the AMY1, AMY2, and AMY3 receptor subtypes (calcitonin receptor combined with RAMP1, 2, or 3) and also the bare calcitonin receptor, which accounts for some downstream effects on bone and calcium handling not seen with pramlintide. The amylin pathway is independent of GLP-1R, GIPR, and the glucagon receptor, which is the basis for its study in combination with GLP-1 agonists. Cagrilintide slows gastric emptying by 40 to 50%, suppresses postprandial glucagon, and acts on both homeostatic and hedonic satiety circuits. In the REDEFINE 1 Phase 3 trial of CagriSema, the combination produced 20.4% body-weight reduction at 68 weeks versus 16.1% for semaglutide alone and 11.8% for cagrilintide alone. Preclinical body-composition data also indicate relative preservation of lean mass.