Quick answer

The molecule that made this era: ~15% mean loss at 2.4 mg weekly (STEP 1), a 20% cardiac-event cut in SELECT, a 24% kidney benefit in FLOW — beaten head-to-head only by tirzepatide (SURMOUNT-5). Three brands, one peptide: Ozempic, Wegovy, Rybelsus.

ClassGLP-1 receptor agonist (injectable peptide; weekly)BrandsOzempic (T2D, 2017) · Wegovy (weight 2021; CV-risk 2024; ages 12+) · Rybelsus (oral, 2019)Dose ladder0.25 → 2.4 mg weekly on the weight label (0.5–2 mg on Ozempic)Half-life≈ 7 daysKey trialsSTEP 1: −14.9% (68 wk) · SELECT: MACE −20% · FLOW: kidney events −24% · STEP 8: beat liraglutide −15.8 vs −6.4 · SURMOUNT-5: lost to tirzepatide −13.7 vs −20.2StatusApproved; the class’s broadest outcome evidence

Deeper data: the trial index holds every figure above with sources; SELECT unpacked, the organ evidence.

Semaglutide is the molecule that made “GLP-1” a household abbreviation — and the only one in the class with proven cardiovascular outcome benefits in people with obesity but without diabetes.

Mechanism and pharmacology

A GLP-1 receptor agonist: it mimics a gut hormone that slows gastric emptying, increases satiety, and improves post-meal insulin response. Half-life is roughly one week, supporting weekly injection — and explaining why the Wegovy label tells patients planning pregnancy to stop at least two months in advance.

The evidence base

STEP 1 (NEJM, 2021): 14.9% average weight loss at 2.4 mg weekly over 68 weeks in adults without diabetes, versus 2.4% on placebo. SELECT (NEJM, 2023): in over 17,000 people with established cardiovascular disease and overweight or obesity — no diabetes — semaglutide 2.4 mg cut major adverse cardiovascular events by 20% versus placebo, the result that earned Wegovy a cardiovascular indication in 2024 (our SELECT explainer). Beyond the heart, trial evidence extends to kidney outcomes and liver disease, mapped in the organ-evidence file. Head-to-head against tirzepatide it lost on average weight — 13.7% vs 20.2% — but averages are not individuals; the nuance is here.

Approved products and dosing

Three brands: Ozempic (type 2 diabetes; 0.5, 1, 2 mg weekly), Wegovy (chronic weight management at 2.4 mg weekly, titrated from 0.25 mg over ~16 weeks; also approved for adolescents 12+ meeting criteria; cardiovascular risk reduction indication added 2024), and Rybelsus — the only FDA-approved oral GLP-1, a daily tablet with strict fasting rules. Higher-dose oral semaglutide for weight management produced strong trial results (the OASIS program) and was under regulatory review as of our last verification — status should be re-checked (oral pipeline file).

Safety essentials

Same class boxed warning on rodent thyroid C-cell tumors and the same contraindications (medullary thyroid carcinoma history, MEN 2). Gastrointestinal effects dominate, concentrated during titration. Unlike tirzepatide, dedicated studies found no clinically significant reduction in oral contraceptive exposure — the pill-interaction warning is tirzepatide-specific. Class cautions on gallbladder disease, pancreatitis, gastroparesis, and pre-surgical disclosure apply; base rates and management live in the side-effects file.

The 2026 cost landscape

Brand list prices run high before insurance; the manufacturer’s direct self-pay channel (NovoCare Pharmacy) and savings offers changed the cash math substantially in 2025 — verify current terms. Compounded semaglutide’s post-shortage legal status is contested (status file). Verified compounded figures, where they exist, are dated in the ledger; the cheapest verified semaglutide rate there today is $119–139/month flat (NexLife — disclosed material connection; see disclosure).

References

Wegovy, Ozempic, Rybelsus prescribing information, Novo Nordisk — novo-pi.com. STEP 1, NEJM 2021; SELECT, NEJM 2023 — full citations in the linked explainers.