Summary

Retatrutide (LY3437943) is Eli Lilly's investigational triple-agonist peptide targeting GIP, GLP-1, and glucagon receptors. In the Phase 3 TRIUMPH programme, it has demonstrated up to 30.3% weight loss at 104 weeks (TRIUMPH-1) and 26.5% weight loss with significant knee osteoarthritis pain improvement (TRIUMPH-4). It is not yet licensed in the UK or any other jurisdiction. Retatrutide represents the leading edge of multi-receptor agonist design in metabolic disease.

Mechanism

Retatrutide is a synthetic peptide that acts as a triple agonist at three metabolic receptors simultaneously: GIP (glucose-dependent insulinotropic polypeptide), GLP-1 (glucagon-like peptide-1), and glucagon receptors. This triple mechanism produces complementary effects: GIP and GLP-1 activation suppress appetite and enhance insulin secretion, while glucagon receptor activation promotes lipolysis, fatty acid oxidation, and hepatic glucose output. The combined effect produces greater weight loss than single- or dual-receptor agonism, with potential direct metabolic effects on liver fat, visceral fat, and inflammation.

Evidence base

Strong evidence. Phase 2 data published in NEJM (2023) showed up to 24.2% weight loss at 48 weeks. Phase 3 TRIUMPH-1 results (announced May 2026) demonstrated 28.3% weight loss at 80 weeks and up to 30.3% at 104 weeks. Phase 3 TRIUMPH-4 results (announced December 2025) showed 26.5% weight loss plus significant knee osteoarthritis pain improvement — the first obesity Phase 3 to demonstrate concurrent OA benefit. UK licensing is pending.

Protocols

Retatrutide is administered via subcutaneous injection. Clinical trial protocols involve dose escalation from a low starting dose (e.g., 1 mg) to target maintenance doses up to 12 mg, with weekly injection frequency. Specific dosing should be referenced from ClinicalTrials.gov and published trial protocols. Not approved for human use in any jurisdiction.

Retatrutide is not licensed by the MHRA for use in the UK. It is an investigational compound in Phase 3 clinical trials. It is not a controlled substance. If approved, it would be classified as a Prescription-Only Medicine (POM) and would require NICE health technology appraisal for NHS funding. For research purposes, retatrutide may be obtained for in vitro or preclinical research under standard research chemical regulations.

Vendor notes

Retatrutide is not commercially available as it is not licensed in any jurisdiction. UK researchers seeking retatrutide for legitimate in vitro or preclinical research should source from established research chemical suppliers with appropriate purity documentation (COAs). It should not be purchased for human consumption.

References

  1. Eli Lilly and Company. 'Lilly's Triple Agonist, Retatrutide, Delivered Weight Loss of 26.5% and Significantly Improved Knee Osteoarthritis Pain in Phase 3 TRIUMPH-4 Trial.' PR Newswire, 11 December 2025.
  2. Eli Lilly and Company. 'Lilly's Triple Agonist, Retatrutide, Delivered Powerful Weight Loss in Pivotal Phase 3 Obesity Trial.' Investor news release, 21 May 2026.
  3. Rheumatology Advisor. 'TRIUMPH-4 Results: Retatrutide Cuts Weight and Knee OA Pain.' 2025.
  4. Jastreboff AM, et al. 'Retatrutide for Obesity in Adults without Diabetes — A Phase 2 Trial.' New England Journal of Medicine, 2023.