Retatrutide is the triple agonist peptide that activates the GIP, GLP-1 and glucagon receptors. In December 2025 Eli Lilly reported topline results from TRIUMPH-4, the first of its Phase 3 trials to read out. The trial enrolled 445 adults with obesity or overweight and knee osteoarthritis, excluding people with type 2 diabetes, and randomised them to retatrutide 9 mg weekly, 12 mg weekly or placebo for 68 weeks (NCT05931367).
The headline result: a mean body-weight reduction of 28.7% at the 12 mg dose and 26.4% at 9 mg, against 2.1% on placebo. That is the largest weight-loss signal reported in a randomised Phase 3 trial of an incretin-based compound to date. The trial also reported a reduction in WOMAC knee-pain scores, a reversal of prediabetes to normoglycaemia in a majority of the affected subgroup, and a fall in LDL cholesterol. The full dataset is pending presentation at a scientific meeting and peer-reviewed publication.
What TRIUMPH-4 does and does not establish
TRIUMPH-4 was a 68-week trial in a specific population: adults with obesity or overweight and knee osteoarthritis, without type 2 diabetes. Its results should not be read as a direct comparison against any licensed medicine. Tirzepatide and semaglutide were tested in different populations under different protocols, and no head-to-head trial has been run. The programme continues: Lilly expects seven further Phase 3 readouts across obesity, type 2 diabetes, obstructive sleep apnoea, chronic low back pain, metabolic dysfunction-associated steatotic liver disease and cardiovascular outcomes. TRIUMPH-1 has since reported a 28.3% mean reduction at 80 weeks on the efficacy estimand.
Regulatory position in the UK
Retatrutide is not licensed anywhere. It has no marketing authorisation from the MHRA and is not available through the NHS or a UK prescription. Under the Medicines Act 1968 and the Human Medicines Regulations 2012, supplying it for human use without a licence is an offence, and it is not a medicine that can lawfully be sold or supplied for personal use. It is discussed here as a research compound, for research use only.
Evidence grade
The Phase 3 data move retatrutide's weight-management evidence toward the top of the field, but the trial record is still short: no long-term safety data, no completed cardiovascular outcomes trial, and no peer-reviewed publication of TRIUMPH-4 at the time of writing. Peptide Data grades on the published record, and that record remains incomplete.
This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.