Retatrutide cut sleep apnoea severity more than placebo in two phase 3 trials

The study

This paper in the New England Journal of Medicine reports two phase 3, double-blind, randomised, placebo-controlled trials. They were nested within larger basket trials of once-weekly subcutaneous retatrutide. The authors describe retatrutide as an investigational triple agonist of the GIP, GLP-1 and glucagon receptors.

Participants were adults with moderate-to-severe obstructive sleep apnoea (OSA) and a body-mass index of at least 27. TRIUMPH-1-OSA enrolled people without type 2 diabetes (243 randomised). TRIUMPH-2-OSA enrolled people with type 2 diabetes (448 randomised). Participants received retatrutide 4 mg, 9 mg or 12 mg, or placebo.

The primary end point was the change in the apnoea-hypopnoea index (AHI) at 80 weeks with 9 mg and 12 mg. The AHI is the average number of apnoeas and hypopnoeas per hour of sleep. The trials were funded by Eli Lilly.

What they found

Baseline mean AHI was 58.6 events per hour in TRIUMPH-1-OSA and 55.9 in TRIUMPH-2-OSA. Mean body weight was 119.6 kg and 115.9 kg.

In TRIUMPH-1-OSA, the AHI fell. The mean change was -34.3 events per hour with 9 mg and -31.7 with 12 mg, against -9.9 with placebo. The difference versus placebo was -24.4 (95% CI, -34.1 to -14.7) for 9 mg and -21.9 (95% CI, -32.2 to -11.5) for 12 mg. The 4 mg dose gave a difference of -13.0 (95% CI, -23.0 to -3.0).

In TRIUMPH-2-OSA, the AHI also fell. The mean change was -24.7 events per hour with 9 mg and -25.4 with 12 mg, against -10.3 with placebo. The difference versus placebo was -14.4 (95% CI, -21.6 to -7.2) for 9 mg and -15.1 (95% CI, -22.5 to -7.7) for 12 mg. The 4 mg dose gave -8.9 (95% CI, -15.9 to -2.0).

These results use a hybrid-treatment estimand. The authors also report intention-to-treat results. For 9 mg and 12 mg, the differences from placebo were -24.7 and -22.5 in TRIUMPH-1-OSA, and -13.9 and -15.0 in TRIUMPH-2-OSA.

Body weight fell with retatrutide. The mean percent change was -12.5 to -22.2% in TRIUMPH-1-OSA and -12.1 to -18.5% in TRIUMPH-2-OSA. With placebo it was -4.8% and -5.6%. The most common adverse events were gastrointestinal.

How much weight to give it

The design is strong. These are phase 3, randomised, double-blind, placebo-controlled trials. The authors concluded that retatrutide gave significantly greater decreases in the AHI than placebo. The 95% confidence intervals for the differences versus placebo do not include zero at any dose in either trial.

The AHI is a measure from sleep studies. It is a surrogate outcome. The abstract does not report effects on daytime symptoms, cardiovascular events or quality of life. It also does not report how many people moved to a lower OSA severity category, or a direct comparison between the doses.

Safety is only briefly covered. The abstract does not report rates of adverse events, stopping of treatment or serious events. The trials were funded by Eli Lilly. Retatrutide also produced large weight loss, and the abstract does not report whether the AHI changes are independent of weight loss. People in the trials had a BMI of at least 27, so the results do not tell us about people with OSA at a lower BMI.

For your clinic

These results show that retatrutide lowered the AHI more than placebo in adults with OSA and a BMI of at least 27, with or without type 2 diabetes. They do not support any change in practice now. The authors call retatrutide investigational, and the source does not say it is available for clinical use.

Read the full paper before drawing conclusions, especially the safety tables, the dropout numbers and the estimand methods. Decisions for individual patients should follow current guidelines and clinical judgement.