- Obstructive sleep apnea is associated with cardiovascular complications and is seen more commonly in individuals with excess adiposity.
- The SURMOUNT OSA phase 3 trials evaluated the safety and efficacy of tirzepatide for the treatment of adults with obstructive sleep apnea and obesity.
- Tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleep-related patient-reported outcomes vs placebo in patients with moderate-to-severe obstructive sleep apnea and obesity.
Obstructive sleep apnea is a condition characterized by disordered breathing during sleep and it is associated with major cardiovascular complications. Individuals with excess adiposity are at an increased risk. Tirzepatide is a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist that selectively binds to and activates both the GIP and GLP-1 receptors. Treatment with tirzepatide has been associated with significant reductions in excess body weight, improvements in blood pressure, and reductions in markers of inflammation and vascular endothelial dysfunction, and may have the potential to be efficacious in persons with obstructive sleep apnea. The SURMOUNT-OSA phase 3 trials (Funded by Eli Lilly; SURMOUNT-OSA ClinicalTrials.gov number, NCT05412004.) assessed the safety and efficacy of tirzepatide for the treatment of adults with obstructive sleep apnea and obesity. The results were presented as a Late-Breaking Symposium at the 84th Scientific Sessions of the American Diabetes Association® (ADA) in Orlando, FL, and were simultaneously published in the New England Journal of Medicine (NEJM).
The SURMOUNT-OSA trials were two 52-week, phase 3, multicenter, parallel-group, double-blind, randomized, controlled trials that were conducted at 60 sites across nine countries to evaluate the efficacy and safety of the maximum tolerated dose of weekly tirzepatide (10 mg or 15 mg) in adults with moderate-to-severe obstructive sleep apnea and obesity. The two trials included 469 individuals with moderate-to-severe OSA and obesity. Study 1 enrolled patients unable or unwilling to use PAP therapy and Study 2 enrolled patients on PAP therapy at baseline. Participants were assigned to receive either tirzepatide or a placebo for 52 weeks. The primary endpoint was the change in the apnea-hypopnea index (AHI), which measures the severity of sleep apnea. Key secondary endpoints included change of sleep apnea specific hypoxic burden (SASHB), CV risk factorsincluding changes in body weight, systolic blood pressure and inflammation (hsCRP), and changes in patient-reported sleep related impairment and sleep disturbance. A total of 469 indivduals were randomly assigned to receive tirzepatide or placebo in trial 1 (234) or trial 2 (235). In trial 1, the mean age of the participants was 47.9 years; mostly male (67.1%) and White (65.8%), with a mean BMI of 39.1 and a mean AHI of 51.5 events per hour. In trial 2, the mean age was 51.7 years; mostly men (72.3%) and White (73.1%), with a mean BMI of 38.7 and a mean AHI of 49.5 events per hour. At baseline, the mean AHI was 51.5 events per hour in trial 1 and 49.5 events per hour in trial 2, and the mean body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) was 39.1 and 38.7, respectively. In trial 1, the mean change in AHI at week 52 was −25.3 events per hour (95% confidence interval [CI], −29.3 to −21.2) with tirzepatide and −5.3 events per hour (95% CI, −9.4 to −1.1) with placebo, for an estimated treatment difference of −20.0 events per hour (95% CI, −25.8 to −14.2) (P<0.001). In trial 2, the mean change in AHI at week 52 was −29.3 events per hour (95% CI, −33.2 to −25.4) with tirzepatide and −5.5 events per hour (95% CI, −9.9 to −1.2) with placebo, for an estimated treatment difference of −23.8 events per hour (95% CI, −29.6 to −17.9) (P<0.001). Significant improvements in the measurements for all prespecified key secondary endpoints were observed with tirzepatide as compared with placebo. The most frequently reported adverse events with tirzepatide were gastrointestinal symptoms but mostly mild to moderate in severity.
“The results of the study have demonstrated the ability of tirzepatide to address both obesity and sleep apnea, offering an effective and comprehensive treatment solution,” said Atul Malhotra, MD, professor of medicine at the University of California San Diego School of Medicine, director of sleep medicine at UC San Diego Health. “Its potential to be used alongside or independently of CPAP could revolutionize how we manage these interconnected conditions. These findings show the potential for the first highly effective drug treatment for sleep apnea.”
https://www.nejm.org/doi/full/10.1056/NEJMoa2404881