Tirzepatide for sleep-disordered breathing in SURMOUNT-OSA: Time course and association with body weight

Obstructive sleep apnea (OSA) is a common disorder with major cardiometabolic and neurocognitive sequelae. It affects up to 1 billion people globally and is frequently attributable to excess weight [1]. Tirzepatide is a once-weekly, dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that is FDA-approved for the treatment of moderate-to-severe OSA in adults with obesity.

The SURMOUNT-OSA program included two 52-week, randomized, double-blind, placebo-controlled, Phase 3 studies (Study 1 and Study 2). The objective of these analyses was to assess time to treatment effects for improvements in apnea-hypopnea index (AHI) and sleep apnea-specific hypoxic burden (SASHB), and how these changes correspond with body weight reduction. We also aimed to investigate weight-dependent and weight-independent effects of tirzepatide treatment for OSA using linear regression analysis.

The results of peripheral AHI (pAHI) and SASHB measurements from WatchPAT 300 in Study 1 were consistent with the polysomnographic (PSG) findings. The tirzepatide-associated improvements in pAHI were significant vs baseline as early as Week 4. However, the estimated treatment difference compared to placebo was not significant until Week 20 for both pAHI and WatchPAT-based SASHB. The magnitude of changes in AHI and SASHB were associated with achieved weight reduction in both studies.

The results from these post hoc analyses provide details regarding the time course of resolution and insights regarding the impact of weight reduction on OSA improvements. Additional research is needed to determine the impact of body weight reduction versus other effects of tirzepatide on the improvements in OSA measures. SURMOUNT-OSA ClinicalTrials.gov number NCT05412004.