Post-Hoc Analysis Links Tirzepatide Treatment to Reduced Daytime Sleepiness in OSA and Obesity

Terri E. Weaver, PhD, RN, FAAN, ATSF, FAASM

(Credit: University of Illinois Chicago)

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.

READ MORE: Post-Hoc Analysis Gives Safety Insights on Switch From Twice-Nightly Oxybate to Once-Nightly 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.

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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