Introduction & Objective: Tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, is approved in the US for treatment of type 2 diabetes and obesity. Tirzepatide showed substantial additional weight reduction vs placebo (PBO) after intensive lifestyle intervention in the phase 3 SURMOUNT-3 (NCT04657016) trial. Here we report the effect of tirzepatide vs PBO on general (Short Form-36 Health Survey Version 2 acute form; SF-36v2) and weight-related (Impact of Weight on Quality of Life-Lite Clinical Trials Version; IWQOL-Lite-CT) mental health outcomes.
Methods: This double-blind, PBO-controlled trial randomized (1:1) adults (N=579) with body mass index ≥30 or ≥27 kg/m2 and ≥1 obesity-related complication (excluding diabetes), who had ≥5% weight reduction after a 12-week (W) intensive lifestyle intervention to receive tirzepatide maximum tolerated dose (MTD; 10 or 15 mg) or PBO once weekly up to W72. Exploratory endpoints assessed were changes from randomization to W72 in SF-36v2 (norm-based) Mental Component Summary (MCS) and its domain scores and IWQOL-Lite-CT Psychosocial composite score using analysis of covariance with the last observation before discontinuation carried forward. Higher scores indicate better health.
Results: At W72, improvement in SF-36v2 MCS score was comparable between tirzepatide MTD and PBO (Least squares mean [LSM] difference [diff] vs PBO: 0.9; p=0.182). Tirzepatide MTD significantly improved SF-36v2 Vitality (LSM diff vs PBO: 2.4), Social Functioning (1.6), Role-Emotional (1.9), and Mental Health (1.5) domain scores (all p<0.05); and IWQOL-Lite-CT Psychosocial composite score (16.0; p<0.001).
Conclusion: In the SURMOUNT-3 trial, adults with obesity or overweight treated with tirzepatide experienced significant improvement in multiple domains of general mental health and weight-related psychosocial function vs PBO after intensive lifestyle intervention.
T. Gibble: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. D. Cao: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. T.D. Forrester: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. J. Brumm: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. A. Chao: Consultant; Eli Lilly and Company. Other Relationship; Eli Lilly and Company. Consultant; Boehringer-Ingelheim. Other Relationship; Weight Watchers International.
This study was funded by Eli Lilly and Company.
