Retatrutide: 25% weight loss at 80 weeks, with knee pain and apnoea gains

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; knee pain and AHI in subgroups

Effect

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

TRIUMPH-1, a phase 3 double-blind trial in NEJM, randomised 2,339 adults with obesity and without diabetes to once-weekly retatrutide (4, 9 or 12 mg) or placebo for 80 weeks. Retatrutide acts on three receptors: GIP, GLP-1 and glucagon.

Mean weight change was −17.6%, −23.7% and −25.0% on the three doses against −3.9% on placebo. In 574 participants with knee osteoarthritis, pain scores fell by about 1.6–1.8 points more than placebo on a 10-point scale. In 243 with obstructive sleep apnoea, the apnoea–hypopnoea index fell by about 22–24 more events per hour. Gastrointestinal effects were the commonest adverse events. The trial was funded by the manufacturer.

Weight loss of this size approaches what is seen after some bariatric procedures. The trial does not yet tell us about cardiovascular outcomes, long-term safety, or what happens when the drug stops.

For now this is trial evidence for an investigational drug. Expect patients to ask about it; the honest answer is that it is not yet a prescribing option and that long-term data are still to come.

• Tell patients who ask that retatrutide is investigational and not yet a prescribing option
• Expect gastrointestinal effects to be the main tolerability issue, as with other incretin drugs
• Note the benefit on knee osteoarthritis pain and sleep apnoea severity, not only on weight
• Remember there are no cardiovascular outcome or post-discontinuation data yet

Why it matters

Drug-induced weight loss is approaching surgical territory, which will change referral conversations.

Don't overread it

Weight, pain and apnoea scores are not cardiovascular events or deaths; those trials have not reported.

The statistics, in plain English

The 21-point placebo-subtracted weight loss at 12 mg is an average; individual responses vary widely. The knee-pain difference of under 2 points on a 10-point scale is modest but meaningful for many patients.

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