Retatrutide Improves Obstructive Sleep Apnea in Adults With Obesity: Study
Australia: The novel triple agonist retatrutide significantly reduced the apnea-hypopnea index (AHI) in adults with obesity or overweight and obstructive sleep apnea (OSA), regardless of type 2 diabetes status, in two parallel randomized clinical trials.
At 80 weeks, AHI reductions versus placebo were 24.4 and 21.9 events/hour with the 9 mg and 12 mg doses, respectively, in patients without diabetes, and 14.4 and 15.1 events/hour, respectively, in those with type 2 diabetes. These findings, published in The New England Journal of Medicine, suggest that retatrutide may offer a promising treatment approach for OSA in people with excess weight.
The findings are from two phase 3 trials, TRIUMPH-1-OSA and TRIUMPH-2-OSA, involving Ronald R. Grunstein of the Woolcock Institute of Medical Research, Macquarie Park, New South Wales, Australia, and colleagues.
OSA is a sleep disorder characterised by repeated interruptions in breathing during sleep. Excess body weight is an important risk factor, and reducing weight may help alleviate disease severity. Retatrutide is an investigational medication that activates three hormone receptors: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon.
The researchers evaluated the efficacy and safety of once-weekly subcutaneous retatrutide in adults with moderate-to-severe OSA and a body mass index of at least 27 kg/m², with or without type 2 diabetes.
A total of 243 participants were enrolled in TRIUMPH-1-OSA, which included individuals without diabetes, while 448 participants with type 2 diabetes entered TRIUMPH-2-OSA. Participants were randomly assigned to receive retatrutide at doses of 4 mg, 9 mg or 12 mg, or a placebo. The primary outcome was the change in AHI after 80 weeks of treatment.
The analysis revealed the following findings:
- Patients without diabetes: AHI decreased by 34.3 events per hour with 9 mg retatrutide and 31.7 events per hour with 12 mg, compared with a reduction of 9.9 events per hour with placebo.
- Patients with type 2 diabetes: AHI declined by 24.7 events per hour with 9 mg and 25.4 events per hour with 12 mg, compared with 10.3 events per hour in the placebo group.
- Weight reduction: Body weight decreased by 12.5% to 22.2% among participants without diabetes and by 12.1% to 18.5% among those with diabetes, depending on the retatrutide dose. The corresponding reductions with placebo were 4.8% and 5.6%, respectively.
- Safety profile: Gastrointestinal symptoms were the most frequently reported adverse events.
The findings demonstrate that retatrutide produced significantly greater improvements in OSA severity than placebo in adults with excess weight, irrespective of diabetes status. The substantial weight reductions observed alongside improvements in AHI suggest that weight loss may contribute to the treatment's effects.
However, retatrutide remains investigational, and further assessment is needed to establish its long-term safety and clinical role. The results support its potential as a treatment option for OSA associated with excess weight, subject to further evidence and regulatory approval.
Reference:
DOI: 10.1056/NEJMoa2611477
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