Retatrutide: about 24–25% weight loss at 80 weeks in obesity without diabetes

Design

Phase 3, randomised, double-blind, placebo-controlled, 80 weeks

Population

2,339 adults with obesity without diabetes

Primary outcome

Percent change in body weight; WOMAC pain and apnoea–hypopnoea index in subgroups

Effect

−23.7% (9 mg) and −25.0% (12 mg) vs −3.9% placebo; differences −19.8 and −21.0 points

TRIUMPH-1 randomised 2,339 adults with obesity and no diabetes to once-weekly retatrutide, a combined GIP, GLP-1 and glucagon receptor agonist, at 4, 9 or 12 mg, or placebo, for 80 weeks. Subgroups with knee osteoarthritis (574) and obstructive sleep apnoea (243) had their own primary outcomes.

Mean weight change was −17.6%, −23.7% and −25.0% across the three doses, against −3.9% with placebo, a placebo-adjusted difference of about 20 to 21 points at the two higher doses. Knee pain on the WOMAC scale fell about 1.6 to 1.8 points more than placebo, and the apnoea–hypopnoea index fell about 22 to 24 more events per hour. Gastrointestinal effects were the commonest adverse events.

Weight loss of this size approaches what has mostly been the territory of bariatric surgery. The trial was conducted in people without diabetes, who typically lose more than those with it, and the abstract does not give discontinuation or lean-mass data. Retatrutide is investigational, with no FDA, EMA or CDSCO approval.

• Expect weight loss in type 2 diabetes to be smaller than in this trial, which excluded people with diabetes.
• Tell patients who ask that retatrutide is not approved anywhere and is available only in trials.
• Ask about knee pain and sleep apnoea symptoms when reviewing weight treatment, since both improved with weight loss here.
• Counsel on gastrointestinal effects before starting any incretin-based drug, as they were the commonest adverse event.

Why it matters

Drug-induced weight loss is approaching surgical scale, which will change who is referred for bariatric surgery and when.

Don't overread it

Weight loss is not an outcome trial: there are no cardiovascular, kidney or mortality data yet.

The statistics, in plain English

The weight results use a treatment-regimen estimand, counting everyone randomised whether or not they kept taking the drug, so they reflect real-world adherence rather than the best case. The knee and sleep apnoea results come from smaller subgroups, which is why the trial reports two ways of handling people who stopped treatment.

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