Cagrilintide + Semaglutide (CagriSema)

What Is Cagrilintide + Semaglutide (CagriSema)?

Cagrilintide + Semaglutide (the research equivalent of Novo Nordisk's CagriSema) is a fixed-ratio blend of two long-acting compounds that suppress appetite through two separate brain circuits. Semaglutide is a long-acting GLP-1 receptor agonist: an analogue of the gut hormone GLP-1 with an albumin-binding fatty-acid side chain that extends its half-life to about seven days. It activates GLP-1R in the pancreas (glucose-dependent insulin release, glucagon suppression), the gut (slowed gastric emptying), and the arcuate nucleus and brainstem appetite centres.

Cagrilintide is a long-acting analogue of amylin, the pancreatic hormone co-released with insulin after a meal. It binds amylin receptors (the calcitonin receptor combined with RAMP1, 2, or 3) in the area postrema of the hindbrain, a satiety gate outside the blood-brain barrier, and is engineered to be non-fibrillating and albumin-bound, unlike the older amylin analogue pramlintide. The amylin pathway is mechanistically distinct from GLP-1R: cagrilintide adds satiety through both homeostatic and hedonic circuits and further slows gastric emptying, while semaglutide drives hypothalamic appetite suppression and peripheral metabolic effects. Two non-overlapping satiety signals produce roughly additive weight reduction, and the amylin arm is associated with relative preservation of lean mass. In the REDEFINE 1 Phase 3 trial, the combination produced 20.4% mean body-weight reduction at 68 weeks against 14.9% for semaglutide alone and 11.5% for cagrilintide alone.