Retatrutide: about a quarter of body weight lost at 80 weeks in obesity

Design

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

Population

2,339 adults with obesity without diabetes (574 with knee osteoarthritis, 243 with obstructive sleep apnoea)

Primary outcome

Percent change in body weight; WOMAC pain in knee osteoarthritis; apnoea-hypopnoea index in sleep apnoea

Effect

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

TRIUMPH-1 assigned 2,339 adults with obesity but not diabetes to once-weekly retatrutide, a GIP, GLP-1 and glucagon receptor agonist, at 4, 9 or 12 mg, or placebo for 80 weeks. Mean weight change was -17.6%, -23.7% and -25.0% across the doses, against -3.9% with placebo.

Two comorbidity endpoints were tested in subgroups. Among 574 participants with knee osteoarthritis, the WOMAC pain score fell by 1.6 to 1.8 points more than placebo at the two higher doses under the hybrid estimand. Among 243 with obstructive sleep apnoea, the apnoea-hypopnoea index fell by about 22 to 24 events per hour more than placebo. Gastrointestinal events were the most common adverse effects.

The drug is investigational and the trial excluded people with diabetes, so it says nothing about glycaemic control. The report is from the manufacturer-funded phase 3 programme; durability after stopping and long-term safety are not addressed in the abstract.

• Retatrutide is investigational; there is nothing to prescribe from this result.
• People with diabetes were excluded, so do not extrapolate the weight figures to them.
• Joint pain and sleep apnoea improved in the prespecified subgroups, which is relevant to how obesity is assessed.
• Gastrointestinal adverse events were the most common, as with other incretin therapies.

Why it matters

Weight loss of about a quarter of body weight in a trial setting raises the bar for what obesity drug therapy may deliver.

Don't overread it

Participants did not have diabetes, and the trial was designed for weight and two obesity complications, not for hard clinical outcomes.

The statistics, in plain English

The knee and sleep apnoea results come from subgroups, analysed with a hybrid estimand that counts stopping treatment as failure. The intention-to-treat figures were similar, which supports their robustness.

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