- Design
- Phase 3, randomised, double-blind, placebo-controlled, 80 weeks
- Population
- 1,152 adults with type 2 diabetes and BMI ≥27, mean BMI 38
- Primary outcome
- Percentage weight change at week 80 (9 mg and 12 mg vs placebo)
- Effect
- −16.8% and −18.8% vs −5.1%; difference at 12 mg −13.8 points (95% CI −15.8 to −11.8)
TRIUMPH-2, published in The Lancet in late September, was a double-blind phase 3 trial at 92 centres in eight countries. It randomised 1,152 adults with type 2 diabetes and a BMI of 27 or more to weekly retatrutide — an agonist at GIP, GLP-1 and glucagon receptors — at 4, 9 or 12 mg, or placebo.
At 80 weeks, weight fell 11.9%, 16.8% and 18.8% on the three doses against 5.1% on placebo; the placebo-adjusted difference at 12 mg was 13.8 points. Diarrhoea affected about a third and nausea up to 28% at higher doses. Hypotension and dysaesthesia were more common than with placebo, and discontinuation for adverse events reached 12% at 9 mg.
Weight loss in diabetes is usually smaller than without it, so these are large numbers. Retatrutide is investigational and not licensed anywhere yet; the dysaesthesia signal is new to the class and worth watching. The trial was industry funded.
- Retatrutide is investigational; it is not available for prescription.
- Expect more gastrointestinal effects than with current GLP-1 agents if it reaches practice.
- Note the dysaesthesia and hypotension signals, which are not typical of the class.
- Patients asking about it can be told it is in trials, not on the market.
Why it matters
A triple agonist may raise the ceiling on drug-induced weight loss in diabetes, with a side-effect profile that differs from the GLP-1 drugs now in use.
Don't overread it
Weight change is a surrogate; this trial did not test cardiovascular or mortality outcomes.
The statistics, in plain English
The treatment-regimen estimand counts everyone randomised, including those who stopped the drug, so it reflects real-world adherence better than an on-treatment analysis. The intervals around each dose effect are well clear of zero.
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