Retatrutide cut the apnoea-hypopnoea index by 14 to 24 events an hour more than placebo

Design

Two phase 3, randomised, double-blind, placebo-controlled trials nested in larger basket trials

Population

691 adults with moderate-to-severe obstructive sleep apnoea and BMI ≥27, without (243) or with (448) type 2 diabetes

Primary outcome

Change in apnoea-hypopnoea index at 80 weeks with 9 mg and 12 mg

Effect

Without diabetes: −24.4 (9 mg) and −21.9 (12 mg) events/h vs placebo; with diabetes: −14.4 and −15.1 events/h vs placebo

Two placebo-controlled phase 3 trials, run inside larger retatrutide programmes, randomised adults with moderate-to-severe obstructive sleep apnoea and a BMI of at least 27 to retatrutide 4, 9 or 12 mg weekly or placebo. TRIUMPH-1-OSA enrolled 243 people without diabetes; TRIUMPH-2-OSA enrolled 448 with type 2 diabetes. Baseline apnoea-hypopnoea index (AHI) was very high, about 56 to 59 events an hour, and mean weight was over 115 kg.

At 80 weeks the AHI fell by 34.3 events an hour on 9 mg in the non-diabetic trial against 9.9 on placebo, a difference of 24.4 (95% CI 14.7 to 34.1). In people with type 2 diabetes the gaps were smaller: 14.4 events an hour on 9 mg and 15.1 on 12 mg. Intention-to-treat results were close to the main estimates. Weight fell by 12 to 22% on retatrutide against about 5% on placebo.

The smaller benefit with diabetes matches what was seen with tirzepatide and with weight loss generally: people with type 2 diabetes tend to lose less weight. For the clinic, the point is not this drug, which is unavailable, but that substantial weight loss moves sleep apnoea severity by a clinically meaningful amount. Positive airway pressure remains the treatment for symptomatic moderate-to-severe disease while weight comes down.

• Ask about snoring, witnessed apnoeas and daytime sleepiness in people with type 2 diabetes and obesity.
• The effect was smaller in people with type 2 diabetes (about 14 to 15 events an hour beyond placebo) than without it (about 22 to 24).
• Baseline severity was high, near 56 to 59 events an hour, so many people improved but did not resolve.
• Gastrointestinal effects were the commonest adverse events, as with other incretin drugs.
• Retatrutide is not approved in India or elsewhere; tirzepatide is the nearest available option with sleep apnoea data.

Why it matters

Incretin-based weight loss is becoming a treatment for sleep apnoea in its own right, which changes who the diabetologist should be asking about snoring and daytime sleepiness.

Don't overread it

Retatrutide is investigational; no regulator has approved it for any indication, and most participants still had sleep apnoea at 80 weeks.

The statistics, in plain English

The AHI counts breathing pauses an hour. A fall of about 24 more events than placebo is large, but starting near 58 most people still had moderate apnoea or worse. The confidence intervals do not cross zero, so the reduction is unlikely to be chance; the wider intervals in the smaller trial reflect fewer participants.

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