0676 The Association Between Tirzepatide and Sleep Architecture: Post-Hoc Analyses from SURMOUNT-OSA

Abstract Introduction In SURMOUNT-OSA, tirzepatide reduced apnea-hypopnea index (AHI), sleep apnea-specific hypoxic burden, and body weight and improved patient-reported outcomes in adults with obesity and moderate-to-severe obstructive sleep apnea (OSA). The association between tirzepatide and sleep architecture has not been investigated. Methods SURMOUNT-OSA included two phase 3 studies evaluating tirzepatide versus placebo for 52 weeks. Study 1 included participants not on positive airway pressure (PAP), while Study 2 participants were on PAP therapy. In these post-hoc analyses, we present changes in sleep architecture (N1, N2, N3, and REM) at week 52 with tirzepatide vs placebo in participants who received ≥1 dose of study drug, using on-treatment data, excluding post-discontinuation data and data after PAP initiation for Study 1 (efficacy analysis set). Results At baseline, in Study 1, the duration (min) of REM sleep was 50.0±29.54, stage N1 66.7±41.10, N2 207.6±60.19, and N3 35.5±37.85. In Study 2, REM sleep duration was 45.2±28.23, N1 77.7±42.07, N2 204.2±58.18, and N3 24.7±29.42. Baseline stage durations were similar across treatment arms. At week 52, the amount of REM sleep (min) increased 14.3±2.93 with tirzepatide and 5.0±3.16 with placebo (p=0.032) in study 1, and 20.0±2.65 with tirzepatide and 1.4±2.98 with placebo (p< 0.001) in study 2. The change in N1 (min) was -12.2±3.08 with tirzepatide and 0.4±3.32 with placebo (p=0.006) in study 1, and -21.1±3.24 with tirzepatide and -0.4±3.62 with placebo (p< 0.001) in study 2. The change in N2 (min) was 0.4±5.05 with tirzepatide and 5.3±5.47 with placebo (p=0.512) in study 1, and 6.2±5.12 with tirzepatide and 9.9±5.73 with placebo (p=0.634) in study 2. The change in N3 (min) was -6.1±2.27 with tirzepatide and -12.0±2.43 with placebo (p=0.076) in study 1, and -1.7±2.27 with tirzepatide and -7.1±2.54 with placebo (p=0.114) in study 2. Conclusion While there were small increases in N2 and decreases in N3 sleep duration, these changes were less pronounced with tirzepatide than with placebo. Overall, these studies indicate that treatment with tirzepatide was associated with an increased amount of REM sleep and a reduction in light N1 sleep. Support (if any) Funded by Eli Lilly and Company.