Semaglutide

Ozempic / Wegovy / Rybelsus

Semaglutide is a GLP-1 receptor agonist engineered for extended half-life (approximately one week) through two structural modifications: substitution of alanine at position 8 (aminoisobutyric acid) to resist DPP-4 degradation, and attachment of a C18 fatty diacid chain that enables reversible albumin binding. Administered as a once-weekly subcutaneous injection (Ozempic for diabetes, Wegovy for obesity) or as a daily oral formulation (Rybelsus) paired with the absorption enhancer SNAC. Its mechanism combines glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, and centrally mediated reductions in appetite via hypothalamic and hindbrain GLP-1 receptors. The STEP trial program demonstrated mean weight reductions of approximately 15% in non-diabetic adults with obesity over 68 weeks. The SELECT trial subsequently showed a 20% reduction in major adverse cardiovascular events in a high-risk population without diabetes — an endpoint that has reshaped cardiometabolic medicine. Common adverse events are GI (nausea, vomiting, constipation) and generally attenuate with gradual dose escalation. Rare but notable signals include gallbladder events, pancreatitis surveillance, and a boxed warning regarding medullary thyroid carcinoma risk based on rodent data.