(3.08) Tirzepatide Improved Health-Related Quality of Life in Adults with Obesity or Overweight: Results from the SURMOUNT-3 phase 3 trial

Tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, is approved in the US for the treatment of type 2 diabetes and obesity. In SURMOUNT-3, a phase 3, randomized, double-blind, placebo-controlled clinical trial, tirzepatide demonstrated substantial additional weight reduction among participants who had achieved ≥5% weight reduction with intensive lifestyle intervention. This analysis determined the impact of tirzepatide versus placebo (PBO) on health-related quality of life (HRQoL) outcomes using SURMOUNT-3 data.

Methods:

Adults (n=579) with body mass index ≥30 or ≥27 kg/m² and ≥1 obesity-related complication (excluding diabetes), who achieved ≥5% weight reduction after a 12-week intensive lifestyle intervention lead-in period were randomly assigned in a 1:1 ratio to receive either maximum tolerated dose (MTD) of tirzepatide (10 or 15 mg) or PBO once weekly for 72 weeks. HRQoL was evaluated from randomization (week (W) 0) to W72 using the 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 the last observation before discontinuation was carried forward. Higher scores reflected better levels of functioning and health. Proportion of participants achieving clinically meaningful improvement (CMI) in the SF-36v2 physical functioning domain score (norm-based; change from baseline ≥5.76) was also assessed. Least squares mean (LSM) difference for tirzepatide versus PBO was calculated using an analysis of covariance model.

Results:

At W72, significantly greater improvements in the SF-36v2 Physical Component Score (PCS) and all domain scores were observed with tirzepatide MTD compared to PBO, with LSM change differences in scores as follows: PCS, 4.0; physical functioning, 3.8; role-physical, 2.5; bodily pain, 3.3; general health, 4.1; vitality, 2.4; social functioning, 1.6; role-emotional, 1.9; and mental health, 1.5; all p< 0.05. Improvements in SF-36v2 Mental Component Score were comparable between the two groups. Proportion of participants achieving CMI (>5.76) in SF-36v2 physical functioning from baseline to W72 was higher for tirzepatide MTD than PBO (29.4% versus 14.8%). LSM change differences in IWQOL-Lite-CT scores for tirzepatide MTD showed significant improvements versus PBO at W72: total, 15.2; physical function composite, 12.8; physical composite, 13.6; and psychosocial composite, 16.0; all p< 0.001.

Discussion/Conclusion:

In the SURMOUNT-3 trial, HRQoL significantly improved with tirzepatide versus PBO in adults with overweight or obesity, following initial weight loss with intensive lifestyle intervention.