0620 Effect of Tirzepatide on Weight Loss in Patients with Obstructive Sleep Apnea and Obesity from SURMOUNT-1

Abstract Introduction Obesity has been estimated to be prevalent in 70% of patients with obstructive sleep apnea (OSA). In SURMOUNT-1, phase 3, 72-week, randomized, double-blind clinical trial in participants with obesity or overweight, those treated with tirzepatide achieved significantly greater weight reduction than placebo. Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. The current post-hoc analysis assessed efficacy of tirzepatide versus placebo on weight reduction in participants with OSA and obesity or overweight. Methods MMRM analysis was conducted in SURMOUNT-1 participants reporting a baseline medical history of “apnoea”, “positive airway pressure therapy” or “sleep apnoea syndrome”. Weight loss measures were assessed in participants on treatment (efficacy estimand) using the modified intention-to-treat analysis set (participants who received at least one dose of study drug (tirzepatide 5mg, 10mg, 15mg, or placebo)). Results There were 197 participants with OSA included in this analysis (tirzepatide 5mg n=41, 10mg n=51, 15mg n=46, and placebo n=59), with baseline age of 48-53 years, body weight 110-122 kg, BMI 39-43kg/m2, presence of hypertension 48-73%, and proportion of females 42-53%. At week 72, estimated treatment difference between tirzepatide and placebo in mean percent weight change was -11.2% (5mg), -18.2% (10mg), and -20.7% (15mg), all P 0.001. Significantly more participants treated with tirzepatide achieved ≥5% body weight reduction (83-98% treated with tirzepatide, 25% with placebo) and ≥10% body weight reduction (46-93% treated with tirzepatide, 15% with placebo) than those treated with placebo (all P 0.001). 27-62% of participants treated with tirzepatide achieved ≥20% body weight reduction compared to 0% in the placebo group (tirzepatide 5mg P=0.006, 10mg and 15mg P 0.001). All doses of tirzepatide significantly reduced waist circumference from baseline to week 72 (-10.6cm, -18.2cm, -18.9cm, all P 0.001). Placebo did not significantly reduce waist circumference at week 72 compared to baseline (-3.5cm, P=0.053). Conclusion Participants with OSA and obesity or overweight treated with tirzepatide had significantly greater weight reduction than those treated with placebo in the SURMOUNT-1 trial. This degree of weight loss would be expected to have a clinically meaningful impact on OSA severity and is being investigated in the SURMOUNT-OSA trial. Support (if any) Eli Lilly and Company.