News|Articles|June 10, 2025
Post-Hoc Analysis Links Tirzepatide Treatment to Reduced Daytime Sleepiness in OSA and Obesity
Author(s)Isabella Ciccone, MPH
Data from a pair of phase 3 trials suggest that tirzepatide treatment may improve patient-reported measures of sleepiness in individuals with obstructive sleep apnea and obesity.
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A new post-hoc analysis of phase 3 trial data presented at the 2025 SLEEP Annual Meeting , held June 8 to 11, in Seattle, Washington, revealed that patients with moderate-to-severe obstructive sleep apnea (OSA) and obesity who were “moderately/very sleepy” and treated with tirzepatide (Zepbound; Eli Lilly and Company) generally showed greater improvements in sleep-related outcomes, particularly among those who did not use positive airway pressure (PAP) therapy.1
Presented by lead author Terri E. Weaver, PhD, RN, FAAN, ATSF, FAASM, Emerita Professor of Biobehavioral Nursing Science at University of Illinois Chicago College of Nursing, the analysis included 2 phase 3 studies (SURMOUNT-1, NCT04184622; SURMOUNT-2, NCT04657003) that assessed tirzepatide compared with placebo in patients with moderate-to-severe OSA and obesity. Study 1 included participants not using PAP therapy at baseline (N = 194), whereas Study 2 included participants who were on PAP therapy (N = 193).
Researchers grouped participants into “not at all/slightly sleepy” (Non-sleepy) or “moderately/very sleepy” (Sleepy) subgroups based on baseline Patient Global Impression of Severity (PGIS) Sleepiness responses. At week 52 in Study 1, authors noted that placebo-adjusted Epworth Sleepiness Scale (ESS) improvements were -1.33 in the Non-sleepy group and -2.18 in the Sleepy group.
Additional findings in Study 1 showed that PROMIS Short Form Sleep-related Impairment (PROMIS-SRI) scores improved by -1.6 and -7.1, respectively, and Functional Outcomes of Sleep Questionnaire (FOSQ) Vigilance domain scores increased by 0.09 and 0.28 in non-sleep and sleepy participants. Notably, investigators reported that half of tirzepatide-treated participants reported being less sleepy (Non-sleepy, 55.0%; Sleepy, 60.9%).
In Study 2, researchers observed that ESS improvements were -1.02 in the Non-sleepy group and -0.57 in the Sleepy group. Additionally, PROMIS-SRI scores improved by -4.3 and -5.6, and FOSQ Vigilance domain scores increased by 0.15 and 0.03, respectively. On the PGIC Sleepiness item, authors reported that 46.6% of Non-sleepy participants and 62.5% of Sleepy participants noted feeling less sleepy at 52 weeks with tirzepatide treatment.
In December 2024, the FDA approved tirzepatide as the first and only prescription treatment for adults with moderate-to-severe OSA and obesity, to be used in combination with a reduced-calorie diet and increased physical activity.2 Tirzepatide's original approval, which came in November 2023, was for the treatment of adults with obesity or overweight who also experience weight-related medical problems. Positive findings from the SURMOUNT-1 (NCT04184622) and SURMOUNT-2 (NCT04657003) trials supported its approval.3,4
With the 2023 approval, it became the first and only dual-activating glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonist for obesity, tackling an underlying cause of excess weight. The expanded indication in moderate-to-severe OSA and obesity was based on positive data from the phase 3 SURMOUNT-OSA trial (NCT05412004).
The SURMOUNT-OSA trial assessed tirzepatide 10 mg or 15 mg in 469 adults with OSA and obesity irrespective of positive airway pressure (PAP) therapy over 52 weeks.4 Among patients not on PAP therapy, tirzepatide was approximately 5 times more effective than placebo in reducing breathing disruptions, achieving 25 fewer hourly breathing disruptions compared with 5 for the placebo cohort. For those on PAP therapy, tirzepatide demonstrated 29 fewer hourly breathing disruptions compared with 6 for placebo.
At the 1-year mark, approximately 42% of adults treated with tirzepatide and 50% of those on tirzepatide plus PAP therapy experienced remission or mild, non-symptomatic OSA. The respective percentages for the placebo-treated cohorts were 16% and 14%, respectively. Adults treated with tirzepatide also saw an average reduction of 18% body weight (~45 lbs), while those on tirzepatide plus PAP therapy lost an average of 20% body weight (~50 lbs), compared with 2% (~4 lbs) and 2% (~6 lbs) on placebo, respectively.
Safety data reported in SURMOUNT-OSA suggested the observed safety profile was similar to the profile reported in the SURMOUNT and SURPASS trials. The most common events related to tirzepatide were gastrointestinal-related and were considered mild to moderate in severity.
REFERENCES
1. Weaver T, Shinde S, Xie C, et al. Measures of Sleepiness Based on Baseline Characterization in Participants: SURMOUNT-OSA Post-Hoc Analysis. Presented at: 2025 SLEEP Annual Meeting; June 8-11; Seattle, WA. ABSTRACT 0777.
2. FDA Approves First Medication for Obstructive Sleep Apnea. News Release. FDA. Published December 20, 2024. Accessed December 23, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea
3. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
4. Garvey WT, Frias JP, Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402(10402):613-626. doi:10.1016/S0140-6736(23)01200-X
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