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Randomized Controlled Trial
. 2025 Nov;33(11):2076-2092.
doi: 10.1002/oby.70011. Epub 2025 Sep 3.

Tirzepatide Associated With Improved Health-Related Quality of Life in Adults With Obesity or Overweight in SURMOUNT-4

Theresa Hunter Gibble  1 , Dachuang Cao  1 , Madhumita Murphy  1 , Irina Jouravskaya  1 , Birong Liao  1 , Harold Edward Bays  2
Affiliations
Randomized Controlled Trial

Tirzepatide Associated With Improved Health-Related Quality of Life in Adults With Obesity or Overweight in SURMOUNT-4

Theresa Hunter Gibble et al. Obesity (Silver Spring). 2025 Nov.

Abstract

Objective: In SURMOUNT-4, participants with obesity or overweight regained substantial weight after tirzepatide withdrawal, whereas continued treatment resulted in additional weight reduction. We evaluated the effect of continued tirzepatide treatment on health-related quality of life (HRQoL) in SURMOUNT-4.

Methods: Participants who achieved tirzepatide maximum tolerated dose (MTD; 10 or 15 mg; N = 670) during a 36-week (W) lead-in period were randomized (1:1) to continue receiving tirzepatide MTD or switch to placebo through W88. HRQoL was assessed using patient-reported outcomes (PROs: SF-36v2, IWQOL-Lite-CT, EQ-5D-5L). Post hoc analysis included changes in PROs by weight reduction categories and baseline Patient Global Impression of Status for physical activity response categories among tirzepatide-treated participants and by weight regain categories in the placebo group.

Results: Tirzepatide treatment was associated with improved PROs from W0 to W36, and these improvements were maintained from W36 to W88 with continued tirzepatide treatment versus placebo. Tirzepatide-treated participants with greater weight reduction and those with physical function limitations at baseline showed numerically greater improvements in PROs. Greater weight regain among participants who switched to placebo was associated with worsening of PROs.

Conclusions: In participants with overweight or obesity, continued tirzepatide treatment was associated with maintaining HRQoL improvement, while treatment withdrawal resulted in worsening of HRQoL.

Trial registration: ClinicalTrials.gov identifier NCT04660643.

Keywords: obesity; patient‐reported outcomes; tirzepatide health‐related quality of life.

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Conflict of interest statement

Theresa Hunter Gibble, Dachuang Cao, Madhumita Murphy, Irina Jouravskaya, and Birong Liao are employees and stockholders of Eli Lilly and Company, Indianapolis, United States. Harold Edward Bays (H.E.B.)'s research site institution has received research grants from 89Bio, Allergan, Alon Medtech/Epitomee, Aligos, Altimmune, Amgen, Anji Pharma, AbbVie, AstraZeneca, Bioage, Bionime, Boehringer Ingelheim, Carmot, Chorus/Bioage, Eli Lilly, Esperion, Evidera, Fractyl, GlaxoSmithKline, HighTide, Home Access, Horizon, Ionis, Kallyope, LG‐Chem, Madrigal, Merck, Mineralys, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Satsuma, Selecta, Shionogi, Skye/Birdrock, TIMI, Veru, Viking, and Vivus. H.E.B. has served as a consultant/advisor for 89Bio, Altimmune, Amgen, Boehringer Ingelheim, Kiniksa, HighTide, Lilly, Novo Nordisk, Regeneron, Veru, Zomagen, and ZyVersa.

Figures

FIGURE 1
FIGURE 1
Effect of tirzepatide versus placebo on general quality of life measured by Short Form‐36 Version 2 Health Survey Acute Form (SF‐36v2). Data are presented as least squares mean change from baseline (Week 0) or randomization (Week 36) using ANCOVA with last observation carried forward for the efficacy analysis set. The SF‐36v2 scores are norm‐based, that is, scores transformed to a scale in which the 2009 US general population has a mean score of 50 and standard deviation of 10. A higher score indicates better health. *p < 0.05, **p < 0.01, ***p < 0.001 versus placebo. MTD, maximum tolerated dose; n, number of participants with baseline and post‐baseline value at the specified time point; SE, standard error. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
Effect of tirzepatide versus placebo on the Physical Functioning domain score of the Short Form‐36 Version 2 Health Survey Acute Form (SF‐36v2; general quality of life survey). Data are presented for the efficacy analysis set: (A) proportion of participants achieving within‐treatment change from baseline (Week 0) or randomization (Week 36); (B) least square mean change from baseline (Week 0) or randomization (Week 36) using ANCOVA with the last observation carried forward. The SF‐36v2 scores are norm‐based, that is, scores transformed to a scale in which the 2009 US general population has a mean score of 50 and standard deviation of 10. A higher score indicates better health. *p < 0.05, **p < 0.01, ***p < 0.001 versus placebo. aA meaningful within‐participant change from the start of open‐label lead‐in (Week 0) or randomization (Week 36) in SF‐36v2 Physical Functioning domain score was defined as an increase of ≥ 5.76 (range 3.84–9.60) using anchor‐based and distribution‐based methods [22]. bParticipants with physical function limitations at baseline were those who rated their physical function as “moderately limited,” or “very much limited,” or “extremely limited” in the Patient Global Impression of Status for physical activity. MTD, maximum tolerated dose; N, number of participants with baseline and post‐baseline value at the specified time point; n, number of participants with physical function limitations at baseline who had baseline and post‐baseline value at the specified time point; SE, standard error. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 3
FIGURE 3
Effect of tirzepatide versus placebo on weight‐related quality of life measured by Impact of Weight on Quality of Life‐Lite‐Clinical Trials Version (IWQOL‐Lite‐CT). Data are presented as least squares mean change from baseline (Week 0) or randomization (Week 36) using ANCOVA with the last observation carried forward for the efficacy analysis set. ***p < 0.001 versus placebo. aFor tirzepatide MTD and placebo groups, within‐treatment change from Weeks 36 to 88 was significant for total and composite (Psychosocial, Physical Function, and Physical) scores (all p < 0.001). MTD, maximum tolerated dose; n, number of participants with baseline and post‐baseline value at the specified time point; SE, standard error. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 4
FIGURE 4
Effect of tirzepatide versus placebo on the Physical Function composite score of the Impact of Weight on Quality of Life‐Lite‐Clinical Trials Version (IWQOL‐Lite‐CT; weight‐related quality of life questionnaire). Data are presented as least squares mean change from baseline (Week 0) or randomization (Week 36) using ANCOVA with the last observation carried forward for the efficacy analysis set. ***p < 0.001 versus placebo. Participants with physical function limitations at baseline were those who rated their physical function as “moderately limited,” or “very much limited,” or “extremely limited” in the Patient Global Impression of Status for physical activity. MTD, maximum tolerated dose; n, number of participants with physical function limitations at baseline who had baseline and post‐baseline value at the specified time point; SE, standard error. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 5
FIGURE 5
Effect of tirzepatide versus placebo on health status measured by EQ‐5D‐5L. Data are presented as least squares mean change from baseline (Week 0) or randomization (Week 36) using ANCOVA with the last observation carried forward for the efficacy analysis set. *p < 0.05, ***p < 0.001 versus placebo. Diff, difference; MTD, maximum tolerated dose; n, number of participants with baseline and post‐baseline value at the specified time point; SE, standard error. [Color figure can be viewed at wileyonlinelibrary.com]
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