Summary

Tirzepatide is a synthetic peptide and dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist developed by Eli Lilly. It is licensed in the UK as Mounjaro (for type 2 diabetes) and Mounjaro/Kimjally (for weight management). In the SURMOUNT programme, tirzepatide achieved up to 22.9% mean weight loss at 72 weeks in adults with obesity. The SURMOUNT-5 head-to-head trial (published in NEJM, 2025) demonstrated tirzepatide's superiority over semaglutide 2.4 mg, with −22.1% vs −15.0% mean weight loss respectively. It is a prescription-only medicine (POM) in the UK.

Mechanism

Tirzepatide is a synthetic 39-amino-acid peptide that acts as a dual agonist at both the GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptors. This dual incretin receptor activation enhances glucose-dependent insulin secretion, suppresses glucagon, delays gastric emptying, and reduces appetite — producing greater weight loss than selective GLP-1 agonism alone.

Evidence base

Tirzepatide has one of the strongest evidence bases among incretin peptide therapies, with multiple Phase 3 trials (SURMOUNT-1 through -5) published in top-tier journals. The SURMOUNT-5 head-to-head trial (NEJM, 2025) provides the first direct comparative data showing tirzepatide's superiority over semaglutide for weight loss (−22.1% vs −15.0% at 72 weeks). The SURMOUNT-1 trial established efficacy in obesity (up to −20.9% at 15 mg), and SURMOUNT-2 confirmed benefits in type 2 diabetes. Evidence quality is rated strong based on multiple large, randomised, double-blind Phase 3 trials with consistent results.

Protocols

In SURMOUNT trials, tirzepatide was administered once weekly via subcutaneous injection. Dose escalation: 2.5 mg for 4 weeks, then increase by 2.5 mg every 4 weeks to target dose (5 mg, 10 mg, or 15 mg). Maximum dose: 15 mg weekly. Gradual titration mitigates gastrointestinal side effects. This is a UK POM — for research/educational context only.

Tirzepatide is a prescription-only medicine (POM) in the UK, licensed by the MHRA as Mounjaro for type 2 diabetes and weight management. Available via NHS prescription under NICE guidelines. Not a controlled substance. The MHRA actively monitors GLP-1 receptor agonists for safety signals (gastrointestinal events, psychiatric adverse effects) via the Yellow Card system. Unlicensed supply without a prescription is illegal under UK medicines legislation.

Vendor notes

As a licensed UK POM, tirzepatide should only be obtained via prescription from a qualified prescriber. Research-grade tirzepatide 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. Jastreboff AM, Aronne LJ, Ahmad NN, et al. "Tirzepatide Once Weekly for the Treatment of Obesity." N Engl J Med, 2022;387:205-216.
  2. Garvey WT, Frias JP, Jastrebroff AM, et al. "Tirzepatide 2.5 mg, 10 mg, or 15 mg Once-Weekly in Patients with Type 2 Diabetes and Obesity (SURMOUNT-2)." Lancet, 2023;401:1927-1937.
  3. Aronne LJ, Bray GA, Frias JP, et al. "Tirzepatide After Intensive Lifestyle Intervention (SURMOUNT-3 and SURMOUNT-4)." Nat Med, 2024.
  4. SURMOUNT-5: Tirzepatide vs Semaglutide in Obesity. N Engl J Med, 2025.
  5. MHRA. "GLP-1 receptor agonists: review of benefits and risks." GOV.UK Drug Safety Updates, 2024–2025.