Retatrutide reduced sleep apnoea severity in two phase 3 trials

Design

Two phase 3, double-blind, placebo-controlled randomised trials

Population

691 adults with moderate-to-severe sleep apnoea and BMI ≥27, with or without type 2 diabetes

Primary outcome

Change in apnoea-hypopnoea index at 80 weeks (9 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

Two double-blind trials, nested within larger retatrutide programmes, randomised adults with moderate-to-severe obstructive sleep apnoea and a BMI of 27 or more to weekly retatrutide (4, 9 or 12 mg) or placebo for 80 weeks. TRIUMPH-1-OSA enrolled 243 people without diabetes; TRIUMPH-2-OSA enrolled 448 with type 2 diabetes. Baseline severity was high, with an average of about 56 to 59 apnoeas and hypopnoeas an hour, and average weight about 116 to 120 kg.

With the 9 and 12 mg doses, the apnoea-hypopnoea index fell by about 22 to 24 more events an hour than placebo in people without diabetes, and by about 14 to 15 more in those with diabetes. Weight fell by 12 to 22% with retatrutide against about 5% with placebo. Gastrointestinal side effects were the most common.

Retatrutide acts on three receptors (GIP, GLP-1 and glucagon) and is investigational. Tirzepatide is already licensed in some countries for sleep apnoea with obesity, so this extends a pattern: substantial weight loss reduces airway collapse.

For now this changes counselling more than prescribing. Many patients remained in the moderate range after treatment, so a drug is unlikely to replace CPAP for most people with severe disease.

• Ask about snoring, witnessed apnoeas and daytime sleepiness in patients with obesity, and refer for a sleep study when present.
• Keep CPAP as first-line therapy for moderate-to-severe sleep apnoea; retatrutide is not approved.
• Re-test sleep apnoea severity after major weight loss before stopping CPAP.
• Discuss weight reduction as a treatment for sleep apnoea, not only a general health goal.

Why it matters

It strengthens the case for treating obesity as a direct treatment of sleep apnoea, not a side project.

Don't overread it

The drug is unapproved and the trials were industry-funded; this does not show fewer cardiovascular events or that CPAP can be stopped.

The statistics, in plain English

The apnoea-hypopnoea index counts breathing pauses per hour; below 5 is normal and 30 or more is severe. A fall of 22 to 24 events more than placebo from a baseline near 58 still leaves many patients with moderate disease. The confidence intervals are wide (for example −34.1 to −14.7), so the precise size of the benefit is uncertain, though clearly real.

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