SURMOUNT-OSA: Tirzepatide Cuts Obstructive Sleep Apnea Severity by 30 Events/Hour

Atul Malhotra, MD
Credit: Kyle Dykes; UC San Diego Health

Results of SURMOUNT-OSA suggest use of tirzepatide (Zepbound) could prove useful in patients with obstructive sleep apnea (OSA) and obesity, with tirzepatide reducing disease severity by approximately 30 events per hour and up to 51% of patients receiving the highest dose of tirzepatide achieving disease remission.

The first GIP/GLP-1 receptor agonist to receive approval from the FDA for type 2 diabetes and obesity, the agent now boasts trial data making its case for another historic indication, with Eli Lilly and Company’s announcement of trial results accompanied by the disclosure of their application to the FDA for tirzepatide in the treatment of moderate-to-severe OSA and obesity. According to Eli Lilly and Company, the FDA granted a Fast Track designation for this indication and submissions for other global regulatory agencies are expected in the coming weeks.^1,2

“In the trials, patients with moderate-to-severe obstructive sleep apnea and obesity treated with tirzepatide experienced about 30 fewer disruptive events every hour of sleep and nearly half achieved disease resolution,” said Atul Malhotra, MD, Peter C. Farrell presidential chair, professor of medicine at University of California San Diego School of Medicine and director of sleep medicine at UC San Diego Health.³ “OSA can be very disruptive to daily life and affects a person’s long-term health when left untreated because it can lead to serious cardiometabolic complications. These data support the efficacy of tirzepatide in adults living with moderate-to-severe OSA and obesity and has the potential to add to our toolbox for OSA treatment.”

Launched in 2022, SURMOUNT-OSA was comprised of 2 substudies conducted at 60 sites in 9 countries to explore the safety and efficacy of tirzepatide at a maximum tolerated dose of 10 or 15 mg relative to placebo therapy among patients with obesity and moderate to severe OSA for 52 weeks. Both substudies included in SURMOUNT-OSA were multicenter, randomized, double-blind trials, with study 1 including patients who were unable or unwilling to use positive airway pressure (PAP) therapy and study 2 including patients who were and planned to stay on PAP therapy during the duration of the trial.^1,3

The primary outcome of interest for both studies was the change in the apnea–hypopnea index (AHI) from baseline to week 52. The substudies also included multiple secondary endpoints, such as percent change in AHI, body weight and changes in hypoxic burden, patient-reported sleep impairment and disturbance, hsCRP, and systolic blood pressure.^1,3

A total of 234 individuals were included in study 1, with 114 receiving tirzepatide and 120 receiving placebo. At baseline, this cohort had a mean age of 47.9 years, 67.1% were male, 65.8% were White, the mean BMI was 39.1 kg/m2, and a mean AHI of 51.5 events per hour.^1,3

A total of 235 individuals were included in study 2, with 120 receiving tirzepatide and 115 receiving placebo. At baseline, this cohort had a mean age of 51.7 years, 72.3% were male, 73.1% were White, the mean BMI was 38.7 kg/m2, and a mean AHI of 49.5 events per hour.^1,3

Presented at the American Diabetes Association (ADA) 84th Scientific Sessions and simultaneously published in the New England Journal of Medicine, primary results of SURMOUNT-OSA indicated tirzepatide achieved all primary and key secondary endpoints for both the efficacy and treatment-regimen estimands.^1,3

In study 1, treatment-regimen estimand revealed use of tirzepatide was associated with a mean change of −25.3 events per hour (95% confidence interval [CI], −29.3 to −21.2) in AHI relative to −5.3 events per hour (95% CI, −9.4 to −1.1) with placebo, which correlates to an estimated treatment difference of −20.0 events per hour (95% CI, −25.8 to −14.2; P <.001). For the efficacy estimand, the change in AHI at week 52 was −27.4 events per hour (95% CI, −31.6 to −23.2) with tirzepatide and −4.8 events per hour (95% CI, −9.3 to −0.3) with placebo, which correlates to an estimated treatment difference of −22.5 events per hour (95% CI, −28.7 to −16.4).^1,3

In study 2, treatment-regimen estimand revealed use of tirzepatide was associated with a mean change of −29.3 events per hour (95% CI, −33.2 to −25.4) in AHI relative to −5.5 events per hour (95% CI, −9.9 to −1.2) with placebo, which correlates to an estimated treatment difference of −23.8 events per hour (95% CI, −29.6 to −17.9), (P <.001). For the efficacy estimand, the change in AHI at week 52 with tirzepatide was −30.4 events per hour (95% CI, −34.3 to −26.5) with tirzepatide and −6.0 events per hour (95% CI, −10.3 to −1.6) with placebo, which correlates to an estimated treatment difference of −24.4 events per hour (95% CI, −30.3 to −18.6).^1,3

In their release, Eli Lilly and Company highlighted disease resolution was achieved by 43.0% of patients receiving the highest dose of tirzepatide in study 1 and 51.5% of patients receiving the highest dose of tirzepatide in study 2.^1,3

Analysis of safety data from the trial indicated the safety profile of tirzepatide among patients in the SURMOUNT-OSA studies was similar to that seen in the SURPASS and SURMOUNT trials, with the most common events being gastrointestinal-related and generally mild to moderate in severity. In study 1, events occurring at a greater frequency than placebo included diarrhea (26.3% vs 12.5%), nausea (25.4% vs 10.0%), and vomiting (17.5% vs 4.2%). In study 2, events occurring at a greater frequency than placebo included diarrhea (21.8% vs 8.8%), nausea (21.8% vs 5.3%), and constipation (15.1% vs 4.4%).^1,3

In a linked editorial published in the Sanjay Patel, MD, of the Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, applauded the trial’s investigators and noted the significance of the results. However, Patel underlined the importance of further analyses and addressing the bevy of questions these results create related to management of OSA.⁴

“Additional analyses of the effects of tirzepatide on a broader range of patient-reported outcome measures by the SURMOUNT-OSA team will be eagerly awaited to evaluate the potential utility of tirzepatide as a sole treatment for obstructive sleep apnea,” Patel wrote.⁴ "If the results of those analyses are promising, the news of an addition of a pharmacologic option to the clinical armamentarium for obstructive sleep apnea will be welcomed by many patients and clinicians alike.”

References:

1. ^{Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. Presented at: American Diabetes Association (ADA) 84th Scientific Sessions. June 21 - 24, 2024. Orlando, FL.}
2. ^{Campbell P. FDA approves Tirzepatide (Zepbound) for Chronic Weight Management. HCP Live. November 8, 2023. Accessed June 21, 2024. https://www.hcplive.com/view/fda-approves-tirzepatide-zepbound-chronic-weight-management.}
3. ^{Eli Lilly and Company. Lilly’s tirzepatide reduced obstructive sleep apnea (OSA) severity, with up to 51.5% of participants meeting the criteria for disease resolution. Eli Lilly and Company.}
4. ^{Patel SR. Entering a New Era in Sleep-Apnea Treatment. N Engl J Med. doi:10.1056/NEJMe2407117}