Obesity Drug Zepbound Approved for Obstructive Sleep Apnea

The US Food and Drug Administration (FDA) has approved the obesity treatment tirzepatide (Zepbound, Eli Lilly) for treating moderate to severe obstructive sleep apnea (OSA) in adults with obesity.

The new indication is for use in combination with reduced-calorie diet and increased physical activity. The once-weekly injectable is the first-ever drug treatment for OSA. Until now, OSA treatment has focused on mechanical support during sleep in the form of positive airway pressure (PAP) therapy.

“Today’s approval marks the first drug treatment option for certain patients with obstructive sleep apnea,” said Sally Seymour, MD, director of the Division of Pulmonology, Allergy, and Critical Care in the FDA’s Center for Drug Evaluation and Research. “This is a major step forward for patients with obstructive sleep apnea.”

Excess weight is a major risk factor for OSA, in which the upper airways become blocked multiple times during sleep and obstruct breathing. The condition causes loud snoring, recurrent awakenings, and daytime sleepiness. It is also associated with cardiovascular disease.

Tirzepatide, a dual glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonist, was initially approved with brand name Mounjaro in May 2022 for the treatment of type 2 diabetes, and as Zepbound for weight loss in November 2023.

The new OSA approval was based on two phase 3, double-blind randomized controlled trials, SURMOUNT-OSA, in patients with obesity and moderate to severe OSA, conducted at 60 sites in nine countries. Results from both were presented in June 2024 at the annual Scientific Sessions of the American Diabetes Association and were simultaneously published in The New England Journal of Medicine.

The first trial enrolled 469 participants who were unable or unwilling to use PAP therapy, while the second included 234 who had been using PAP for at least 3 months and planned to continue during the trial. In both, the participants randomly received either 10 mg or 15 mg of tirzepatide or placebo once weekly for 52 weeks.

At baseline, 65%-70% of participants had severe OSA, with more than 30 events/h on the apnea-hypopnea index (AHI) and a mean of 51.5 events/h. By 52 weeks, those randomized to tirzepatide had 27-30 fewer events/h compared with 4-6 fewer events/h for those taking placebo. In addition, significantly more of those on tirzepatide achieved OSA remission or severity reduction to mild.

Those randomized to tirzepatide also averaged up to 20% weight loss, significantly more than with placebo. “The improvement in AHI in participants with OSA is likely related to body weight reduction with Zepbound,” according to an FDA statement.

Side effects of tirzepatide include nausea, diarrhea, vomiting, constipation, abdominal discomfort and pain, injection site reactions, fatigue, hypersensitivity reactions (typically fever and rash), burping, hair loss, and gastroesophageal reflux disease.

In an editorial accompanying The New England Journal of Medicine publication of the SURMOUNT-OSA results, Sanjay R. Patel, MD, wrote “The potential incorporation of tirzepatide into treatment algorithms for obstructive sleep apnea should include consideration of the challenges of adherence to treatment and the imperative to address racial disparities in medical care.”

Patel, who is professor of medicine and epidemiology at the University of Pittsburgh, Pittsburgh, and medical director of the UPMC Comprehensive Sleep Disorders program, pointed out that suboptimal adherence to CPAP therapy has been a major limitation, but that adherence to the GLP-1 drug class has also been suboptimal.

“Although adherence to tirzepatide therapy in the SURMOUNT-OSA trial was high, real-world evidence suggests that nearly 50% of patients who begin treatment with a GLP-1 receptor agonist for obesity discontinue therapy within 12 months. Thus, it is likely that any incorporation of tirzepatide into treatment pathways for obstructive sleep apnea will not diminish the importance of long-term strategies to optimize adherence to treatment.”

Moreover, Patel noted, “racial disparities in the use of GLP-1 receptor agonists among patients with diabetes arouse concern that the addition of tirzepatide as a treatment option for obstructive sleep apnea without directly addressing policies relative to coverage of care will only further exacerbate already pervasive disparities in clinical care for obstructive sleep apnea.”

Patel reported consulting for Apnimed, Bayer Pharmaceuticals, Lilly USA, NovaResp Technologies, Philips Respironics, and Powell Mansfield, Inc. He is a fiduciary officer of BreathPA.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape Medical News, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X @MiriamETucker.