5183 Tirzepatide Improved Health-Related Quality of Life in People with Obesity or Overweight: Results from SURMOUNT-4 Phase 3 Trial

Abstract Disclosure: T.M. Gibble: Employee; Self; Employment and stockholder, Eli Lilly and Company. D. Cao: Employee; Self; Employment and stockholder, Eli Lilly and Company. M. Murphy: Employee; Self; Employment and stockholder, Eli Lilly and Company. I. Jouravskaya: Employee; Self; Employment and stockholder, Eli Lilly and Company. B. Liao: Employee; Self; Employment and stockholder, Eli Lilly and Company. Background: Tirzepatide is approved in the U.S. for treatment of type 2 diabetes (T2D) and obesity. In the phase 3 SURMOUNT-4 trial with randomized withdrawal of tirzepatide maximum tolerated dose (MTD) after the first 36 weeks, continuing tirzepatide for 88 weeks led to a mean weight reduction of 25.3% from baseline compared to 9.9% for those who switched to placebo (PBO).1 This analysis evaluated the effects of tirzepatide versus PBO on health-related quality of life (HRQoL) outcomes using the SURMOUNT-4 trial data. Methods: Adults (n=783) with body mass index ≥30 or ≥27 kg/m2 and ≥1 obesity-related complication (excluding T2D) were enrolled in an open-label lead-in period to receive tirzepatide once weekly for 36 weeks, escalated to MTD (10 mg or 15 mg). At week (W) 36, 670 participants were randomized 1:1 to continue tirzepatide MTD (n=335) or were switched to PBO (n=335) for 52 weeks. HRQoL was evaluated using Short Form-36 Version 2 Health Survey (SF-36 v2) acute form and Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT), where last observation before discontinuation was carried forward. Higher scores reflected better levels of functioning. Least square means (LSM) and estimated treatment differences (ETD) between tirzepatide versus PBO were calculated using an analysis of covariance model. Proportion of people achieving clinically meaningful improvement (CMI) in SF-36v2 physical functioning score (change from baseline ≥5.76) was also assessed. Results: LSM changes in SF-36 v2 and IWQOL-Lite-CT scores were comparable during lead-in (W0 to W36) between people randomized to tirzepatide and PBO. Significant improvements were observed from W36 to W88 in SF-36v2 Physical Component Score (PCS), Mental Component Score (MCS), and all domains for tirzepatide versus PBO, with LSM (ETD) as follows: PCS, 54.9, 53.1 (1.8); MCS, 54.6, 52.9 (1.7); physical functioning, 54.2, 51.6 (2.6); role-physical, 54.3, 53.3 (1.1); bodily pain, 54.7, 53.1 (1.6); general health, 56.7, 54.1 (2.6); vitality, 57.0, 55.4 (1.6); social functioning, 54.2, 52.9 (1.3); role-emotional, 53.0, 51.1 (1.9), and mental health, 55.4, 52.9 (2.4), respectively; all p<0.05. Proportion of people achieving CMI (%) in SF-36v2 physical functioning from W0 to W88 was higher for tirzepatide than those who switched to PBO (≥ 5.76, 52.0 and 36.2). Tirzepatide showed significant improvements in IWQOL-Lite-CT scores versus PBO from W36 to W88, with LSM scores (ETD) as follows: total, 86.4, 75.3 (11.1); psychosocial, 87.7, 75.6 (12.1); physical function, 85.7, 76.2 (9.4); and physical, 83.8, 74.7 (9.1), respectively; all p<0.001. Conclusion: In SURMOUNT-4 trial, adults with overweight or obesity continuing on tirzepatide showed significant and sustained improvements in HRQoL versus those switching to PBO. 1Sattar N. 59th Annual Meeting European Association for the Study of Diabetes; Oct 2023; Germany. Presentation: 6/3/2024