Semaglutide
FDA-approved GLP-1 agonist — the most effective pharmacological weight loss agent in history (15–20% body weight reduction).
Research facts
| Half-life | ~7 days |
|---|---|
| Route | SubQ (weekly) / Oral |
| Typical dose | 0.25–2.4 mg/week SubQ (Wegovy titration) |
| Frequency | Once weekly |
| Solvent | Pre-filled pen |
| pH | N/A — commercial formulation |
| Stability | Refrigerated (2–8°C) |
Mechanism of action
Semaglutide is a long-acting GLP-1 receptor agonist — a fatty acid-modified analogue of endogenous GLP-1 with C18 lipid chain conjugated to a modified lysine residue, enabling albumin binding and 7-day half-life. It acts on GLP-1 receptors in the hypothalamus and brainstem to reduce appetite and food intake, slows gastric emptying, and directly stimulates pancreatic beta cells to release insulin in a glucose-dependent manner. The STEP trial series (the largest weight loss RCT programme in history) demonstrated 14.9–17.4% body weight loss at 68 weeks with Wegovy dose.
Documented effects (research-model)
- S-tier: FDA-approved with massive RCT evidence base (STEP, SUSTAIN, SOUL trials)
- 14.9–17.4% body weight loss in STEP clinical trials
- Significant cardiovascular risk reduction (SELECT trial: 20% reduction in MACE)
- T2DM glucose control and HbA1c reduction
- Non-alcoholic fatty liver disease reduction
- Obstructive sleep apnoea improvement (SURMOUNT-OSA)
Research protocols
| Protocol | Dose | Frequency | Cycle | Vial |
|---|---|---|---|---|
| Wegovy (obesity) | Titrate: 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg/week | Once weekly SubQ | Ongoing — discontinuation leads to weight regain | Wegovy pre-filled pen |
Research context only. Not medical advice. Consult a qualified healthcare professional before any protocol decision.
Synergies
- Tirzepatide N/A
Tirzepatide (GLP-1 + GIP dual agonist) is considered the superior successor — not combined. - Retatrutide N/A
Retatrutide (GLP-1 + GIP + glucagon triple agonist) is the next-generation evolution — not combined.
Myths & misconceptions
Evidence gaps
- Long-term (>5 year) weight maintenance and cardiovascular outcomes still accumulating.
- Optimal cessation protocol to minimise rebound not established.
- Lean mass preservation strategies during treatment need more definitive RCT data.
Safety notes
FDA-approved with comprehensive post-marketing safety data. Common: nausea, vomiting, diarrhoea, constipation (usually dose-limiting). Rare: pancreatitis, gallbladder disease, medullary thyroid carcinoma risk (C-cell tumour signal in rodents — theoretical risk in humans). Not for use in MEN2 or personal/family history of medullary thyroid carcinoma.
Biomarkers to monitor
Primary-source citations
- PMID 33667417 — Once-weekly semaglutide in adults with overweight or obesity (STEP 1) (N Engl J Med. 2021)
- PMID 39153289 — SELECT: Semaglutide and cardiovascular outcomes in obesity without diabetes (N Engl J Med. 2023)
Frequently asked
What is Semaglutide?
Semaglutide (Ozempic / Wegovy — GLP-1 Receptor Agonist) is a research compound classified in our library as Tier S — Overwhelming human data — approved and prescribed.. FDA-approved GLP-1 agonist — the most effective pharmacological weight loss agent in history (15–20% body weight reduction).
What is the evidence tier for Semaglutide?
We classify Semaglutide as Tier S: Overwhelming human data — approved and prescribed. See our full peptide evidence tiers explainer for how we assign S/A/B/C/D.
What is the research dose of Semaglutide?
For Semaglutide, typical research dose is 0.25–2.4 mg/week SubQ (Wegovy titration), route is SubQ (weekly) / Oral, half-life is ~7 days. Protocols vary by research goal — see the protocols section on this page for standard and advanced dosing schedules. Research use only, not medical advice.
Is Semaglutide safe?
FDA-approved with comprehensive post-marketing safety data. Common: nausea, vomiting, diarrhoea, constipation (usually dose-limiting). Research context only — no compound on this site is approved for human therapeutic use unless explicitly noted.