(3.10) Tirzepatide Improves Health-Related Quality of Life in Participants With Obesity or Overweight and Type 2 Diabetes: Results From Phase 3 SURMOUNT-2 Trial
Objective : Tirzepatide is a once weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved in the US for treatment of type 2 diabetes (T2D) and obesity. Tirzepatide showed substantial weight reduction vs placebo (PBO) in participants with obesity or overweight and T2D in the phase 3, randomized, double-blind, PBO-controlled SURMOUNT-2 (NCT04657003) trial. Here we report the effect of tirzepatide vs PBO on health-related quality of life (HRQoL) outcomes.
Methods: Adult participants (N=938) with a body-mass index of ≥27 kg/m² and T2D (glycated hemoglobin 7%–10%) were randomized (1:1:1) to receive subcutaneous tirzepatide 10 mg, tirzepatide 15 mg or PBO every week (W) up to W72, with a reduced-calorie diet and increased physical activity. HRQoL outcomes were assessed at W72 using change from baseline in Short Form-36 Version 2 Health Survey acute form (SF-36v2; norm-based scores) and Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) scores. Response rate for clinically meaningful improvement (CMI) in SF-36v2 Physical Functioning (PF) domain norm-based score (change from baseline ≥5.76) was also assessed. Analyses were performed in the modified intent-to-treat population. Least squares mean (LSM) difference (diff) for pairwise comparison was calculated using analysis of covariance with last observation carried forward for missing data imputation.
Results: Significant improvement (p< 0.001) in SF-36v2 Physical Component Summary (PCS) score was seen in tirzepatide 10 mg (LSM diff vs PBO: 1.8) and tirzepatide 15 mg (2.5) groups at W72. Participants in tirzepatide 15 mg group showed significant improvements (p< 0.05) in SF-36v2 PF (LSM diff vs PBO: 2.3), Bodily Pain (2.1), General Health (2.6), Vitality (1.3), and Social Functioning (1.3) domain scores. Improvements in SF-36v2 Mental Component Summary (MCS), Role-Physical, Role-Emotional and Mental Health domain scores were comparable between tirzepatide (10 mg and 15 mg) and PBO groups. Response rate for CMI in SF-36v2 PF domain score was greater with tirzepatide(10 mg: 34.2%; 15 mg: 35.6%) vs PBO (24.1%). In tirzepatidegroups (10 mg and 15 mg), significant improvements (p< 0.001) were seen in IWQOL-Lite-CT Total score (LSM diff vs PBO: 5.0 and 6.5), and Psychosocial (4.0 and 5.8), Physical Function (6.9 and 7.8) and Physical (6.6 and 7.7) composite scores at W72, respectively.
Discussion/Conclusion: In the SURMOUNT-2 trial, HRQoL significantly improved across physical and psychosocial aspects of functioning in tirzepatide- vs PBO-treated participants with obesity or overweight and T2D.
