Retatrutide: up to a quarter of body weight lost in phase 3

Design

Phase 3, randomised, double-blind, 80 weeks

Population

2,339 adults with obesity, without diabetes

Primary outcome

Percent change in body weight (with osteoarthritis pain and sleep apnoea in subgroups)

Effect

-25.0% with 12 mg vs -3.9% placebo (difference -21.0 percentage points)

TRIUMPH-1 randomised 2,339 adults with obesity but without diabetes to once-weekly retatrutide, a triple agonist of the GIP, GLP-1 and glucagon receptors, at 4, 9 or 12 mg, or placebo, for 80 weeks.

Weight loss was large and dose-dependent: 17.6% at 4 mg, 23.7% at 9 mg and 25.0% at 12 mg, against 3.9% with placebo. The trial also met co-primary endpoints in two subgroups: knee osteoarthritis pain fell more than with placebo, and the apnoea-hypopnoea index dropped by around 32 to 34 events per hour at the higher doses against about 10 with placebo. Gastrointestinal effects were the commonest adverse events.

The headline figure takes the weight-loss ceiling for incretin-based therapy higher again. Retatrutide is investigational and not yet approved, so the practical point for now is to expect patients to ask about it, and to be able to place it against available agents rather than to prescribe it.

• 2,339 adults with obesity, without diabetes, randomised to retatrutide 4, 9 or 12 mg or placebo for 80 weeks.
• Mean weight loss was 25.0% at 12 mg versus 3.9% with placebo.
• Knee osteoarthritis pain improved more than with placebo in a 574-patient subgroup.
• The apnoea-hypopnoea index fell by about 32 to 34 events per hour at higher doses.
• Gastrointestinal effects were the most common adverse events.

Why it matters

It pushes the expected ceiling of drug-induced weight loss higher and brings osteoarthritis and sleep apnoea into the frame.

Don't overread it

Retatrutide is investigational and not yet approved; these are trial-condition results and gastrointestinal side-effects were common.

The statistics, in plain English

A 25.0% versus 3.9% difference, about 21 percentage points, is far larger than chance and larger than most earlier incretin trials. The osteoarthritis and sleep-apnoea benefits were separate pre-specified endpoints, so they stand on their own rather than being read off the weight result.

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