Retatrutide, Eli Lilly’s once-weekly “triple agonist”, has now reported topline results from four Phase 3 trials. Together they make it the most effective weight-loss compound tested at this scale so far. Here is what each TRIUMPH trial found, what the side-effect data looks like, and where that leaves the UK.
What is retatrutide?
Retatrutide (LY3437943) activates three hormone receptors at once: GIP, GLP-1 and glucagon. Tirzepatide (Mounjaro) hits the first two. Adding glucagon-receptor activity is thought to raise energy expenditure and increase liver fat burning, on top of the appetite suppression of GLP-1 drugs.
The 2023 Phase 2 study in the New England Journal of Medicine first drew attention: participants on the 12 mg dose lost an average of 24.2% of their body weight in 48 weeks, with no plateau in sight.
TRIUMPH-4: the first Phase 3 readout (December 2025)
TRIUMPH-4 enrolled adults with obesity and knee osteoarthritis. At 68 weeks, the 12 mg dose produced an average weight loss of 28.7%, the first Phase 3 confirmation that the Phase 2 numbers would hold up in a larger trial.
TRIUMPH-1: the pivotal obesity trial (May 2026)
TRIUMPH-1 is the headline study: 2,339 adults with obesity or overweight plus at least one weight-related condition (but not diabetes), randomised to 4 mg, 9 mg or 12 mg once weekly, or placebo, for 80 weeks. Average starting weight was 112.7 kg, with an average BMI of 40.
| 80 weeks (efficacy estimand) | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| Mean weight change | −19.0% | −25.9% | −28.3% | −2.2% |
| Lost ≥25% of body weight | 27.8% | 52.9% | 62.5% | 2.2% |
| Lost ≥30% of body weight | 15.3% | 37.9% | 45.3% | 0.5% |
| Waist change | −16.3 cm | −21.8 cm | −24.1 cm | −3.6 cm |
Under the stricter treatment-regimen estimand, which counts everyone randomised including people who stopped, the 12 mg result was −25.0%.
A pre-specified 104-week extension in participants with a starting BMI of 35 or more reached −30.3% on 12 mg (about 38.6 kg / 85 lb). Lilly reported no weight-loss plateau.
TRIUMPH-2 and TRIUMPH-3 (July 2026)
- TRIUMPH-2 (1,152 adults with type 2 diabetes and obesity): weight loss of 12.7%, 19.1% and 20.8% on 4, 9 and 12 mg, against 4.0% on placebo, at 80 weeks. HbA1c fell by up to 1.6 percentage points from a 7.7% baseline. People with diabetes typically lose less weight on incretin drugs, so these results are strong for this group.
- TRIUMPH-3 (1,949 adults with a BMI of 35+ and established cardiovascular disease): 21.6% (9 mg) and 22.6% (12 mg) weight loss against 3.2% on placebo, plus improvements in blood pressure, lipids and inflammation markers.
Side effects
The side-effect profile looks like a stronger version of the GLP-1 class, with one new signal:
- Gastrointestinal effects were the most common. At 12 mg in TRIUMPH-1: nausea 42.4% (placebo 14.8%), diarrhoea 32.0%, constipation 26.1% and vomiting 25.3%. These mostly occurred during dose escalation.
- Dysaesthesia, an abnormal or unpleasant skin sensation, affected 12.5% on 12 mg versus 0.9% on placebo. Lilly says it was generally mild to moderate and mostly resolved while participants stayed on treatment.
- Discontinuation due to adverse events rose with dose: 4.1% (4 mg), 6.9% (9 mg) and 11.3% (12 mg), versus 4.9% on placebo.
These are topline figures from company press releases. Full peer-reviewed publications will give the detailed safety picture.
What happens next?
Lilly has said it plans to submit retatrutide to the US FDA by the first quarter of 2027, with submissions in other countries to follow. Still to come:
- TRIUMPH-5, a head-to-head trial against tirzepatide
- TRIUMPH-Outcomes, a long-term cardiovascular and kidney outcomes study
- Results in obstructive sleep apnoea and knee osteoarthritis pain
What it means in the UK
Retatrutide has no MHRA marketing authorisation, and Lilly hasn’t announced a UK filing date. On a typical timeline after an early-2027 US submission, UK approval is unlikely before late 2027 or 2028, and NHS access, which needs a NICE appraisal, would come later still.
Until then, retatrutide in the UK is available only inside clinical trials or from suppliers selling it as a research chemical. If you are comparing those suppliers, our UK supplier ranking and price tracker show who publishes independent test results and what each charges per mg.
Sources
- Eli Lilly: TRIUMPH-1 topline results (21 May 2026)
- Eli Lilly: TRIUMPH-2 and TRIUMPH-3 results (23 July 2026)
- PharmExec: Retatrutide delivers up to 22.6% weight loss in two new Phase III trials
- Jastreboff AM et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. NEJM 2023
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