Summary

Semaglutide is a synthetic GLP-1 receptor agonist developed by Novo Nordisk, marketed as Ozempic (type 2 diabetes), Wegovy (weight management), and Rybelsus (oral). In the STEP programme, semaglutide 2.4 mg achieved −14.9% mean weight loss at 68 weeks. The SELECT trial demonstrated a 20% reduction in major cardiovascular events. The SURMOUNT-5 head-to-head trial (NEJM, 2025) showed tirzepatide produced superior weight loss (−22.1% vs −15.0% for semaglutide), positioning semaglutide as highly effective but no longer the most efficacious incretin for weight loss. It is a prescription-only medicine (POM) in the UK.

Mechanism

Semaglutide is a modified GLP-1 (7-37) analogue with an Aib substitution at position 8 (conferring DPP-4 resistance) and a C18 fatty diacid chain (promoting albumin binding and extending half-life to ~165 hours). It selectively agonises the GLP-1 receptor, enhancing glucose-dependent insulin secretion, suppressing glucagon, delaying gastric emptying, and reducing appetite via central pathways.

Protocols

In STEP trials, semaglutide was administered once weekly via subcutaneous injection with gradual dose escalation: 0.25 mg → 0.5 mg → 1.0 mg → 1.7 mg → 2.4 mg (maintenance for Wegovy). Maximum: 2.4 mg weekly (Wegovy) or 2.0 mg (Ozempic). Oral formulation (Rybelsus): 3 mg → 7 mg → 14 mg daily. Gradual titration mitigates GI side effects. This is a UK POM — for research/educational context only.

Semaglutide is a prescription-only medicine (POM) in the UK, licensed by the MHRA as Ozempic (T2D), Wegovy (weight management), and Rybelsus (oral, T2D). Available via NHS prescription under NICE guidelines. Not a controlled substance. The MHRA actively monitors GLP-1 receptor agonists for safety signals (gastrointestinal events, pancreatitis, psychiatric adverse effects) via the Yellow Card system. The MHRA has issued warnings about counterfeit semaglutide products. Unlicensed supply without a prescription is illegal under UK medicines legislation.

Vendor notes

As a licensed UK POM, semaglutide should only be obtained via prescription from a qualified prescriber. The MHRA has issued warnings about counterfeit semaglutide products entering the UK supply chain. Research-grade semaglutide is available from select UK research chemical suppliers for in vitro and preclinical research purposes only — not for human use. See vetted vendor listings for suppliers with appropriate research-grade product lines.

References

  1. Wilding JPH, Batterham RL, Calanna S, et al. "Semaglutide 2.4 mg Once Weekly in Adults with Overweight or Obesity (STEP 1)." N Engl J Med, 2021;384:989.
  2. Davies M, Færch L, Jeppesen OK, et al. "Semaglutide 2.4 mg Once a Week in Adults with Overweight or Obesity and Type 2 Diabetes (STEP 2)." Lancet, 2021;397:971.
  3. Garvey WT, Batterham RL, Bhatta M, et al. "Two-Year Effects of Semaglutide in Adults with Overweight or Obesity (STEP 5)." Nat Med, 2022;28:2089.
  4. SURMOUNT-5: Tirzepatide vs Semaglutide in Obesity. N Engl J Med, 2025.
  5. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)." N Engl J Med, 2023;389:2221.
  6. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2). N Engl J Med, 2025;393:648-659. PubMed: 40544432.
  7. MHRA. "GLP-1 receptor agonists: review of benefits and risks." GOV.UK Drug Safety Updates, 2024–2025.