P017 Association Between Tirzepatide and Fatigue and Functioning Based on Baseline Characterization: SURMOUNT-OSA Trials

Abstract Introduction Daytime sleepiness, a common symptom of obstructive sleep apnea (OSA), can be measured via multiple patient-reported outcome questionnaires. It is hypothesized that tirzepatide may reduce daytime sleepiness, as it showed significant improvements in the apnea hypopnea index in the SURMOUNT-OSA trials. Methods Two phase-3 studies evaluated the efficacy of the maximum tolerated dose of tirzepatide (10 or 15 mg) versus placebo in participants with moderate-to-severe OSA and obesity. Study 1 participants were not on positive airway pressure (PAP) therapy while Study 2 participants were on PAP therapy. Post-hoc analyses were performed to compare changes in sleep-related measures between tirzepatide and placebo groups, based on baseline sleepiness levels. Results In Study 1 (n = 194) and Study 2 (n = 193), placebo adjusted changes from baseline to week 52 with tirzepatide treatment were seen on ESS (0.57-2.18), PROMIS-SRI (1.6-7.1) and FOSQ Vigilance (0.03-0.28), with generally greater improvements in those that were sleepy at baseline. The majority of participants treated with tirzepatide reported that they were less sleepy at week 52. Over half of the participants treated with tirzepatide reported reduced sleepiness. Conclusion These post-hoc analyses found that participants treated with TZP who were “moderately/very sleepy” at baseline generally showed greater improvement on the ESS, PROMIS-SRI, and FOSQ Vigilance domain than those “not at all/slightly sleepy”. The majority of of all TZP-treated participants reported improvements in overall sleepiness, despite sleepiness at baseline.