- Design
- Phase 3, randomised, double-blind, placebo-controlled, 80 weeks
- Population
- 1,152 adults with BMI ≥27 and type 2 diabetes on non-insulin therapy
- Primary outcome
- Percentage change in body weight at 80 weeks (9 mg and 12 mg)
- Effect
- −18.8% vs −5.1%; difference −13.8% (95% CI −15.8 to −11.8) at 12 mg
TRIUMPH-2, in The Lancet (29 September), randomised 1,152 adults with obesity and type 2 diabetes across eight countries to once-weekly retatrutide 4, 9 or 12 mg or placebo for 80 weeks. Retatrutide acts on GIP, GLP-1 and glucagon receptors. Mean BMI was 38 and baseline HbA1c 7.7%.
Weight fell 11.9%, 16.8% and 18.8% across the doses against 5.1% with placebo — placebo-adjusted differences of 6.9% to 13.8%. Gastrointestinal effects were common; nausea reached 28% at 12 mg. Hypotension (up to 6%) and dysaesthesia (up to 7%) were more frequent than with placebo, and discontinuation for adverse events reached 12% at 9 mg.
Weight loss in people with diabetes is typically smaller than in those without, so these figures are substantial. The drug is not approved anywhere, and the dysaesthesia signal needs explaining.
- Placebo-adjusted weight loss reached about 14% at 80 weeks on the highest dose
- Expect nausea and diarrhoea in about a quarter to a third of patients on higher doses
- Hypotension and skin dysaesthesia were more frequent than with placebo — new signals to watch
- Not approved by any regulator; patients asking can be told it remains investigational
Why it matters
A triple agonist could push weight loss in diabetes towards what has only been seen without it.
Don't overread it
No cardiovascular or long-term outcome data yet, and it is not approved.
The statistics, in plain English
The 12 mg difference of −13.8% (95% CI −15.8 to −11.8) is precise and well beyond chance. The 'treatment regimen' estimand counts everyone randomised, including those who stopped the drug, so it reflects real-world use more than on-drug results do.
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