Semaglutide

Semaglutide is a synthetic analogue of human glucagon-like peptide-1 (GLP-1) with 94% amino acid sequence homology to native GLP-1, engineered with key modifications that extend its half-life to approximately 7 days, enabling once-weekly dosing. These modifications include an amino acid substitution at position 8 (Aib for Ala) to resist DPP-4 degradation, and acylation with a C18 fatty diacid chain at position 26 to promote albumin binding and slow renal clearance. Semaglutide activates the GLP-1 receptor to enhance glucose-dependent insulin secretion, suppress glucagon, delay gastric emptying, and reduce appetite through central nervous system satiety pathways. While effective as a single-mechanism GLP-1 agonist, research has shown that dual-agonist approaches like tirzepatide (GIP/GLP-1) may produce superior outcomes in body weight reduction. Semaglutide remains one of the most significant peptide therapeutics developed in metabolic research.