Tirzepatide yields numerically greater PROM improvements in OSA patients with higher baseline fatigue, sleepiness, or poor sleep quality

Obstructive Sleep Apnea (OSA) is a chronic condition characterized by recurrent upper airway collapse during sleep, leading to intermittent hypoxia and sleep fragmentation. It is strongly associated with obesity and significantly impairs quality of life through symptoms like fatigue, excessive daytime sleepiness, and poor sleep quality. Current standard-of-care, such as positive airway pressure (PAP), often faces adherence challenges, and while weight loss is beneficial, effective pharmacological options are limited. Tirzepatide, a dual GLP-1R and GIPR agonist, has shown significant efficacy in weight reduction and is being investigated for its potential to improve OSA and related patient-reported outcomes.

These post-hoc analyses examined data from SURMOUNT-OSA, two 52-week randomized, placebo-controlled studies (Study 1: no PAP; Study 2: PAP users). Participants with moderate-to-severe OSA and obesity were treated with tirzepatide 10/15mg or placebo. Participants were stratified by self-reported baseline severity of fatigue (Non-fatigued/Fatigued), sleepiness (Non-sleepy/Sleepy), snoring (Non-snoring/Snoring), and sleep quality (Good/Poor). Changes in patient-reported outcome measures (PROMs) and objective assessments (AHI, SASHB, weight, OSA remission) from baseline to Week 52 were evaluated within each subgroup.

Across both studies, tirzepatide treatment consistently led to greater improvements in PROMs and objective assessments compared to placebo. In Study 1 (non-PAP users), tirzepatide-treated participants in the Fatigued subgroup experienced numerically greater improvements in several PROMs compared to the Non-fatigued subgroup. Specifically, FOSQ Activity Level improved by an LSM difference from placebo of 0.33 vs 0.05, SF-36v2 Vitality by 8.5 vs 1.0, and SF-36v2 General Health scores by 6.2 vs 1.4. The Sleepy subgroup showed numerically greater improvements versus the Non-sleepy subgroup in PROMIS Short-Form Sleep-Related Impairment 8a scores, with an LSM difference of -7.1 vs -1.6. > Participants with Poor sleep quality at baseline also saw numerically greater improvements in PROMIS Short-Form Sleep Disturbance scores, with an LSM difference of -5.8 vs -1.2, compared to the Good sleep quality subgroup. Changes in PROMs were similar across both snoring subgroups. Importantly, tirzepatide was associated with similar improvements in objective assessments (AHI, SASHB, weight, OSA remission) across all symptom severity subgroups in both studies, indicating broad efficacy beyond subjective improvements.