Semaglutide

Semaglutide is a synthetic GLP-1 receptor agonist with 94% homology to endogenous GLP-1. It has been structurally modified to resist dipeptidyl peptidase-4 (DPP-4) degradation and to enhance albumin binding, extending its half-life to approximately 165 hours. This enables onceweekly subcutaneous dosing (Ozempic® for type 2 diabetes, Wegovy® for obesity) or daily oral dosing (Rybelsus®). Mechanism of Action GLP-1 receptor activation - Stimulates glucose-dependent insulin secretion via pancreatic β-cells while suppressing glucagon from α-cells. Central appetite regulation - Activates GLP-1 receptors in the hypothalamus and area postrema to reduce food intake and enhance satiety. Delayed gastric emptying - Promotes prolonged fullness and reduced caloric intake. Multi-organ protection - Enhances β-cell preservation, cardiovascular and liver function, and neuroprotection through BDNF upregulation and reduced neuroinflammation. Structural modifications - Aminoisobutyric acid substitution at position 8 protects against DPP-4, and a fatty diacid side chain at lysine 26 allows albumin binding for extended pharmacokinetics.