Semaglutide
Long-acting glucagon-like peptide-1 receptor agonist with C18 diacid lipid modification enabling once-weekly dosing; stimulates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite via CNS GLP-1R signaling.
Semaglutide is a structural analog of native glucagon-like peptide-1 (GLP-1), with two amino-acid substitutions and a C18 diacid fatty acid side chain attached via a γGlu-2×OEG spacer to lysine-26. The lipid modification confers high-affinity binding to serum albumin, producing a circulating half-life of approximately one week and enabling once-weekly subcutaneous administration.
Mechanistically, Semaglutide acts as a full agonist at the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor expressed prominently in pancreatic beta cells, gastrointestinal smooth muscle, and hypothalamic appetite-regulating nuclei (notably the arcuate nucleus). Receptor activation stimulates glucose-dependent insulin secretion, suppresses inappropriate glucagon release, slows gastric emptying, and produces central anorectic effects via POMC/CART neuron activation. The metabolic effects are intentionally glucose-dependent, reducing the hypoglycemia risk seen with insulin-secretagogues.
Semaglutide is approved for type 2 diabetes (Ozempic, oral Rybelsus) and chronic weight management (Wegovy). PharmaKinetics catalogs Semaglutide for research and educational reference; clinical use should be undertaken only under licensed medical supervision.