CagrilintideCagrilintide + Semaglutide (CagriSema) Dual-Class Research Reference by QSC Peptides

Cagrilintide is a fatty acid-modified amylin analog with a ~7-day half-life, targeting amylin receptors (AMYR1 and AMYR3) — which are heterodimers of the calcitonin receptor (CTR) plus RAMP1 or RAMP3. Amylin is co-secreted with insulin from pancreatic β-cells at meals, acting as a post-meal satiety signal distinct from the GLP-1 pathway.

Combined with semaglutide as CagriSema, Cagrilintide provides access to two completely independent appetite pathways — amylin (area postrema, brainstem) and GLP-1 (hypothalamus, vagal afferents) — producing greater weight reduction than either compound alone.

Cagrilintide (Amylin Pathway)

• Area postrema / NTS: Amylin acts on CTR/RAMP complexes in circumventricular organs, signaling meal size and satiety through brainstem circuits independent of GLP-1R
• Gastric emptying: Slows gastric emptying independent of GLP-1R, prolonging post-meal satiety
• Glucagon suppression: Post-meal amylin receptor activation suppresses glucagon secretion from α-cells
• Adiposity signals: Amylin interacts with leptin signaling pathways in the hypothalamus

Why Combining Amylin + GLP-1R (CagriSema) Is Additive

The amylin (AMYR) and GLP-1 (GLP-1R) appetite pathways are anatomically and mechanistically distinct. AMYR acts primarily on brainstem circuits; GLP-1R acts primarily on hypothalamic and vagal circuits. Co-activation of both pathways produces additive appetite suppression, explaining the ~22–25% weight reduction of CagriSema vs ~15–17% for semaglutide alone.