Cagrilintide vs GLP-1 (7-37)

Long-acting amylin analogue; acts on amylin/calcitonin receptors to prolong satiety; synergistic with semaglutide in CagriSema combination

Cagrilintide is a long-acting synthetic amylin analogue under clinical development for obesity, designed to mimic the satiety-promoting and gastric-emptying-reducing actions of the endogenous beta-cell hormone amylin. By activating amylin receptors in the hindbrain, cagrilintide reduces caloric intake and body weight, and the drug is also being co-developed with the GLP-1 receptor agonist semaglutide (CagriSema) to target multiple appetite-regulating pathways simultaneously. Phase 2 randomized controlled trials published in The Lancet have demonstrated meaningful weight reduction in people with overweight and obesity, establishing proof of concept for both monotherapy and combination approaches. Cagrilintide is an investigational compound that has not yet received FDA approval; it remains in late-stage clinical development as of 2025.

Binds GLP-1 receptors in the pancreas, gut, and brain. Stimulates glucose-dependent insulin secretion and suppresses glucagon. Central GLP-1 receptor activation reduces food intake via hypothalamic pathways.

GLP-1(7-37) is the native 30-amino-acid active form of glucagon-like peptide 1, an endogenous incretin hormone secreted by intestinal L-cells in response to nutrient ingestion, that acts at GLP-1 receptors throughout the body to stimulate glucose-dependent insulin secretion, suppress glucagon release, slow gastric emptying, reduce appetite, and protect beta-cell mass; it is the endogenous ligand underlying the pharmacology of the GLP-1 receptor agonist drug class. The GLP-1 receptor is expressed on pancreatic beta cells, hypothalamic appetite-regulating neurons, gastric enteric neurons, and cardiovascular tissue; GLP-1(7-37) activates cAMP/PKA signaling in beta cells to potentiate insulin release strictly during hyperglycemia, providing intrinsic hypoglycemia protection, and centrally reduces caloric intake through satiety signaling. A randomized controlled trial of continuous subcutaneous native GLP-1 infusion in patients with type 2 diabetes demonstrated significant reductions in plasma glucose and appetite, confirming receptor-mediated effects of the native peptide in humans; the peptide's very short plasma half-life of approximately 2 minutes due to rapid DPP-IV degradation makes continuous infusion the only practical administration route for the native form. Native GLP-1(7-37) has no FDA approval as a drug; FDA-approved GLP-1 receptor agonists — including semaglutide, liraglutide, dulaglutide, and tirzepatide — are chemically modified DPP-IV-resistant analogs developed to overcome the native peptide's pharmacokinetic limitations, and research-grade native GLP-1 is used exclusively as a tool compound in metabolic pharmacology studies.