Semaglutide
Approved as Ozempic (subcutaneous, 2017, type 2 diabetes), Rybelsus (oral, 2019, type 2 diabetes), and Wegovy (subcutaneous 2.4 mg, 2021, chronic weight management; expanded to cardiovascular risk reduction in 2024).
Semaglutide mimics endogenous GLP-1; an Aib8 substitution blocks DPP-4 degradation, and an albumin-binding fatty-diacid conjugate extends its half-life from roughly 2 minutes (native GLP-1) to about a...
Sequence
Mechanism of Action
Semaglutide mimics endogenous GLP-1; an Aib8 substitution blocks DPP-4 degradation, and an albumin-binding fatty-diacid conjugate extends its half-life from roughly 2 minutes (native GLP-1) to about a week, enabling weekly dosing. It stimulates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite via hypothalamic action. It carries a boxed warning for thyroid C-cell tumors based on rodent carcinogenicity data (human relevance undetermined) and is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. In the pivotal STEP 1 trial, it produced 14.9% mean weight reduction versus 2.4% for placebo at 68 weeks; the SELECT cardiovascular outcomes trial found a reduced composite rate of cardiovascular death, heart attack, or stroke in adults with obesity and existing cardiovascular disease.