Changes in patient-reported outcomes and objective assessments based on baseline symptom severity in SURMOUNT-OSA: post-hoc analyses.

STUDY

objectivesThese post-hoc analyses of SURMOUNT-OSA evaluated patient-reported outcome measures (PROMs) and objective assessments, considering participants' baseline characterization of fatigue, sleepiness, snoring, and sleep quality. MATERIALS AND

methodsSURMOUNT-OSA included two 52-week randomized, placebo-controlled studies of tirzepatide (10/15 mg) in participants with moderate-to-severe obstructive sleep apnea (OSA) and obesity (Study 1: participants not using positive airway pressure [PAP]; Study 2: participants using PAP). Participants were grouped 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 PROMs and objective assessments from baseline to Week 52 were assessed per subgroup.

resultsIn both studies, tirzepatide treatment was consistently associated with greater improvements in PROMs and objective assessments than placebo. In Study 1, tirzepatide-treated participants in the Fatigued subgroup had numerically greater improvements versus Non-fatigued subgroup in Functional Outcomes of Sleep Questionnaire Activity Level (least-square means [LSM] difference from placebo: 0.33 vs. 0.05), SF-36v2 Vitality, (8.5 vs. 1.0), and SF-36v2 General Health scores (6.2 vs. 1.4). The Sleepy subgroup showed numerically greater improvements versus Non-sleepy subgroup in Patient-Reported Outcomes Measurement Information System (PROMIS) Short-Form Sleep-Related Impairment 8a scores (LSM difference: -7.1 vs. -1.6) while the Poor sleep quality subgroup had numerically greater improvements versus Good sleep quality subgroup in PROMIS Short-Form Sleep Disturbance scores (LSM difference: -5.8 vs. -1.2). Changes in PROMs were similar in both snoring subgroups. Study 2 patterns were generally consistent with Study 1. Tirzepatide treatment was associated with similar improvements in objective assessments (apnea-hypopnea index, sleep apnea-specific hypoxic burden, weight, OSA remission) across all symptom severity subgroups in both studies.

conclusionsAcross subgroups, tirzepatide treatment was associated with greater improvements in PROMs than placebo. Participants with worse fatigue, sleepiness, and sleep quality at baseline generally had larger improvements on related PROMs than those with milder symptoms. Tirzepatide treatment was also associated with greater improvements in objective assessments versus placebo, though these changes were generally similar across baseline symptom severity subgroups. CLINICAL

trial registrationRegistered at ClinicalTrials.gov under "Obstructive Sleep Apnea Master Protocol GPIF: A Study of Tirzepatide (LY3298176) in Participants With Obstructive Sleep Apnea (SURMOUNT-OSA)"; https://clinicaltrials.gov/study/NCT05412004; registration number: NCT05412004.