Semaglutide is a GLP-1 receptor agonist with 94% amino acid homology to native GLP-1 and a ~7-day half-life. It is FDA-approved as Ozempic (T2D, 2 mg max) and Wegovy (obesity, 2.4 mg max).
Titration Schedule
Start 0.25 mg subcutaneously once weekly × 4 weeks → 0.5 mg × 4 weeks → 1.0 mg × 4 weeks → 1.7 mg × 4 weeks → 2.4 mg maintenance (Wegovy protocol). Slow titration minimizes GI side effects.
STEP Clinical Trial Results
STEP-1 (NEJM 2021): 14.9% mean body weight reduction at 68 weeks. STEP-4: 6.9% additional weight loss when continuing vs 6.9% weight regain when switching to placebo. SELECT (NEJM 2023): 20% reduction in major cardiovascular events.
Mechanism of Action
Semaglutide activates GLP-1 receptors in the hypothalamus (appetite suppression), pancreatic beta cells (insulin secretion), and gut (gastric emptying delay). The fatty acid chain modification enables albumin binding and the extended 7-day half-life.