Semaglutide — questions, answered plainly.

Semaglutide is an acylated 31-residue analogue of GLP-1(7-37) with a long-chain (C18) fatty diacid side chain. The lipidation provides high albumin binding affinity and a long half-life suitable for once-weekly subcutaneous dosing (Ozempic, Wegovy) or daily oral dosing (Rybelsus).

All three contain semaglutide as the active ingredient. Ozempic is FDA-approved for type 2 diabetes (subcutaneous, weekly). Wegovy is approved for chronic weight management (subcutaneous, weekly, different dose ladder). Rybelsus is the oral once-daily formulation for type 2 diabetes.

STEP is the Phase III clinical trial programme that supported semaglutide's obesity indication. STEP 1 (Wilding 2021, NEJM, PMID 33567185; n=1961) reported mean body weight reduction of 14.9% with semaglutide 2.4 mg versus 2.4% with placebo over 68 weeks.

Wadden et al. 2021 (JAMA, PMID 33625476; n=611) studied semaglutide 2.4 mg combined with intensive behavioural therapy in adults with overweight or obesity. Mean body weight reduction was 16.0% versus 5.7% with placebo + behavioural therapy over 68 weeks.

Garvey et al. 2022 (Nature Medicine, PMID 36216945; n=304) reported sustained 15.2% body weight reduction with semaglutide 2.4 mg versus 2.6% with placebo over 104 weeks (STEP 5). Long-term outcomes beyond two years are addressed in additional post-marketing surveillance not cited on this profile.

Glucagon-like peptide-1 is an endogenous incretin hormone secreted by intestinal L-cells in response to nutrient intake. It augments glucose-dependent insulin secretion, suppresses inappropriate glucagon release, delays gastric emptying, and contributes to satiety signalling — the pharmacology semaglutide and other GLP-1 agonists are designed around.

This profile cites three STEP Phase 3 trials in adults with overweight/obesity. The diabetes-indication (SUSTAIN programme) and cardiovascular-outcome (SELECT) trials are large and well-known but not cited as primary references here. Clinical use is a medical decision with a qualified healthcare professional.