Abstract
Introduction
In SURMOUNT-2, a phase 3, randomized clinical trial, tirzepatide treatment resulted in clinically meaningful reduction in bodyweight among people with obesity or overweight and T2D. The current analysis evaluated the effects of tirzepatide treatment on self-reported health-related quality of life (HRQoL) outcomes among SURMOUNT-2 participants.
Methods
SURMOUNT-2 participants were randomly assigned (1:1:1) to receive either tirzepatide 10 mg (n = 312), tirzepatide 15 mg (n = 311), or placebo (n = 315) for 72 weeks as an adjunct to diet and exercise. Self-reported HRQoL was assessed in terms of changes from baseline to week 72 in Short Form-36 Version 2 Health Survey acute form (SF-36v2), Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT), EQ-5D 5-level Version (EQ-5D-5L) Health State Index (UK) and associated EQ visual analog scale (VAS), and Patient Global Impression of Status (PGIS) for Physical Activity. Post hoc analyses evaluated changes in HRQoL outcomes by categorical percent weight reduction targets (> 0 to < 5%, ≥ 5%, ≥ 10%, ≥ 15%, ≥ 20%, ≥ 25%, and ≥ 30%) and by self-reported baseline physical function limitations (based on PGIS) among tirzepatide-treated participants.
Results
At week 72, tirzepatide treatment was associated with significantly larger improvements than placebo in the SF-36v2 Physical Component Summary score, SF-36v2 physical functioning, bodily pain, general health, vitality, and social functioning domain scores, all IWQOL-Lite-CT scores, and EQ VAS score. Tirzepatide-treated participants who achieved greater weight reduction targets showed numerically larger improvements in HRQoL scores relative to those with lower percent weight reduction. For all HRQoL measures, participants with physical function limitations at baseline showed greater improvements than those without limitations.
Conclusions
Tirzepatide treatment was associated with improved self-reported HRQoL outcomes compared with placebo among people with obesity or overweight with T2D. Participants achieving greater bodyweight reductions and those with physical function limitations at baseline showed greater improvements in HRQoL.
Clinical Trial Registration Number for SURMOUNT-2
Supplementary Information
The online version contains supplementary material available at 10.1007/s13300-025-01723-w.
Keywords: Chronic weight management, HRQoL, Patient-reported outcomes
Key Summary Points
| Why carry out this study? |
| The SURMOUNT-2 Phase 3 clinical trial investigated the effects of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, on bodyweight reduction in participants with obesity or overweight and type 2 diabetes (T2D). |
| Previous studies have shown that people with obesity have reduced health-related quality of life (HRQoL). In this study, we evaluated the effects of tirzepatide treatment on patient-reported HRQoL outcomes among SURMOUNT-2 participants. |
| What was learned from the study? |
| In the SURMOUNT-2 trial, participants with obesity and T2D treated with tirzepatide reported significant improvements in HRQoL outcomes versus placebo, both in terms of physical and psychosocial aspects of functioning. |
| Among tirzepatide-treated participants, those who reported physical limitations at baseline and those with greater bodyweight reduction reported greater improvements in HRQoL. |
Introduction
Obesity and type 2 diabetes (T2D) are chronic conditions of public health concern and rising global prevalence [1–3]. Both conditions are linked in their pathogenesis, which can influence disease state progression [4]. Obesity and overweight are significant risk factors for developing T2D, and conversely, a vast majority of individuals with T2D are affected by obesity or overweight [5, 6]. Incretin-based treatments for T2D and obesity result in improved glucose-dependent insulin secretion, appetite suppression, and delayed gastric emptying, thereby leading to improved glycemic control and bodyweight reduction [7].
Tirzepatide is a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptor agonist [8, 9]. It is approved in several countries, including the USA, as an adjunct to diet and exercise for the treatment of adults with T2D and in combination with a reduced-calorie diet and increased physical activity to reduce excess bodyweight and maintain weight reduction long-term in adults with obesity or overweight with at least one weight-related comorbid condition [8–10]. The SURMOUNT phase 3 program evaluated the efficacy and safety of tirzepatide as an adjunct to lifestyle intervention for chronic weight management [11–14]. In the SURMOUNT-2 trial (NCT04657003), tirzepatide treatment led to clinically meaningful bodyweight reduction versus placebo among participants living with obesity or overweight and T2D [10]. The mean percent change from baseline in bodyweight at week 72 was −12.8% with tirzepatide 10 mg, −14.7% with tirzepatide 15 mg, and −3.2% with placebo. More tirzepatide-treated participants (79–83%) achieved ≥ 5% bodyweight reduction relative to participants who received placebo (32%; p < 0.0001) [12].
Obesity and T2D have demonstrated a significant negative impact on health-related quality of life (HRQoL), often leading to limitations in physical functioning and deterioration of mental health and social relationships [3, 15–19]. Prior studies have established that a high body mass index (BMI) is associated with a decline in quality of life (QoL), including HRQoL and work productivity [20–23]. Furthermore, existing literature in various settings and populations has also demonstrated the positive association between bodyweight reduction, HRQoL, and QoL-related improvements [21, 24, 25].
As clinical interest in tirzepatide grows and for improved long-term management of obesity, it becomes imperative for healthcare providers (HCPs) to understand how weight loss associated with tirzepatide can impact the physical and mental aspects of HRQoL. Patient-reported outcomes (PROs) that measure HRQoL capture the patients’ perspectives on their health and well-being and provide valuable insights into their day-to-day functioning that can inform treatment-related decisions [26, 27]. This analysis aims to evaluate the effects of weight loss associated with tirzepatide treatment on self-reported HRQoL outcomes among participants in the SURMOUNT-2 clinical trial.
Methods
Study Design and Population
SURMOUNT-2 (NCT04657003) was a 72-week, multicenter, randomized, double-blind, phase 3 clinical trial that evaluated the safety and efficacy of 10 and 15 mg tirzepatide compared with placebo among adults (18 years or older) with a BMI of 27 kg/m2 or higher and a T2D diagnosis [12]. Participants were on stable T2D therapy (either diet and exercise alone or oral antihyperglycemic medications) for at least 3 months before screening. Full eligibility criteria and study design have been previously reported [12]. After a 3-week screening period, participants were randomly assigned (1:1:1) to receive either tirzepatide 10 mg, tirzepatide 15 mg, or placebo for 72 weeks, in addition to lifestyle intervention, followed by a 4-week safety follow-up period without treatment [12]. This multicountry trial was conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines and the Declaration of Helsinki and was approved by local institutional review boards. All participants provided written informed consent prior to the study.
Study Outcomes
HRQoL outcomes were included in SURMOUNT-2 as prespecified secondary endpoints and were assessed at week 72 or early treatment discontinuation. Outcomes included change from baseline in the Short Form-36 Version 2 Health Survey acute form (SF-36v2), Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT), EuroQol 5 Dimension 5 Level Version (EQ-5D-5L) Health State Index and associated EQ visual analog scale (VAS), and the Patient Global Impression of Status (PGIS) for Physical Activity. The response rate for participants achieving meaningful within-patient change (MWPC) in the SF-36v2 physical functioning domain was also calculated [28].
Post hoc analyses were performed to assess the relationship between bodyweight reduction and associated improvements in HRQoL outcomes following tirzepatide treatment. Improvements in HRQoL outcomes were evaluated by categorical percent weight reduction targets (≥ 5%, ≥ 10%, ≥ 15%, ≥ 20%, ≥ 25%, and ≥ 30%). Participants were also categorized into groups with or without self-reported baseline physical function limitations (based on PGIS for physical activity) to investigate improvements in HRQoL outcomes by baseline status.
PRO Measures
The SF-36v2 is a 36-item generic PRO measure used to assess general health status. The measure assesses eight domains (physical function, role-physical, bodily pain, general health, vitality, social functioning, role—emotional, and mental health) and provides two health component summary scores (physical and mental health). Items are answered on Likert scales of varying lengths (3-point, 5-point, or 6-point). Scores are norm based, with a mean score of 50 and standard deviation of 10. Higher scores indicate better levels of function and/or better health [29].
The IWQOL-Lite-CT is a 20-item, obesity-specific PRO measure designed for use in clinical trials for adults living with obesity or overweight, both with and without T2D. This measure assesses two primary domains: the physical composite (7 items) and the psychosocial composite (13 items); a 5-item subset of the physical composite, the physical function composite, is also assessed. Items are rated on a 5-point frequency (“never” to “always”) or a 5-point truth (“not at all true” to “completely true”) scale. Overall scores range from 0 to 100, with higher scores associated with better HRQoL [30, 31].
The EQ-5D-5L is a generic 5-item measure assessing mobility, self-care, usual activities, pain/discomfort, and anxiety/depression [32]. A health profile and a single health state index value can be derived. The index value ranges between < 0 (where 0 is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). In addition, a VAS records the respondent’s self-rated health status on a vertical graduated scale from 0 to 100.
The PGIS for Physical Activity is a participant-rated assessment of current limitations on physical activity due to health and is rated on a 5-point scale ranging from “not at all limited” to “extremely limited.” Responses to the PGIS for Physical Activity were used to identify participants with moderately, very, or extremely limited physical function at baseline.
Statistical Analysis
Statistical analyses were conducted using SAS v.9.4. Analyses were performed in the efficacy analysis set (randomized participants, excluding off-treatment data). Least squares mean (LSM) difference (standard error (SE)) for pairwise comparison between tirzepatide groups and placebo was calculated using analysis of covariance (ANCOVA) with the last observation carried forward (LOCF) for imputation of missing data at week 72. Variables included in the model were baseline (i.e., at randomization) score, stratification factors (country, sex, and type of antihyperglycemic medication at baseline), and treatment (type III sum of squares). MWPC threshold for the SF-36v2 physical functioning domain was empirically derived to be 5.76 (norm based).
In post hoc analyses among tirzepatide-treated participants, mean changes in SF-36v2 norm-based, IWQOL-Lite-CT, and EQ-5D-5L scores from baseline to week 72 by percent weight reduction targets (≥ 5%, ≥ 10%, ≥ 15%, ≥ 20%, ≥ 25%, and ≥ 30%), as well as for the group of participants with percent weight reduction < 5% (including participants with weight gain) and for participants with versus without physical function limitations at baseline were descriptively summarized.
Results
Participant demographics and key characteristics across treatment arms have been previously reported [12]. A total of 938 participants were randomly assigned to treatment groups (tirzepatide 10 mg, n = 312; tirzepatide 15 mg, n = 311; placebo, n = 315), of whom 859 completed the study (10 mg, n = 296; 15 mg, n = 282; placebo, n = 281). The mean age of participants was 54.2 years; 50.7% were female, 75.7% were white, and 59.8% were Hispanic or Latino. The mean (SD) baseline bodyweight was 100.7 (21.1) kg, and the mean (SD) BMI was 36.1 (6.6) kg/m2.
HRQoL Outcomes for Tirzepatide Versus Placebo
At week 72, the tirzepatide 10 and 15 mg treatment groups showed significantly greater improvements in the SF-36v2 Physical Component Summary (PCS) score versus placebo (p < 0.001 for both). Participants in the tirzepatide 15 mg group showed significant improvements (p < 0.05) in SF-36v2 physical functioning, bodily pain, general health, vitality, and social functioning domain scores versus placebo. Improvements in SF-36v2 mental component summary, role-physical, role-emotional, and mental health domain scores were comparable between tirzepatide (10 mg and 15 mg) and placebo groups (Fig. 1a). The proportion of participants achieving MWPC (≥ 5.76) in the SF-36v2 physical functioning score from baseline to week 72 was numerically higher with tirzepatide 10 mg (34.2%) and 15 mg (35.6%) than with placebo (24.1%; Fig. 2).
Fig. 1.
Mean change in patient-reported outcomes from baseline to week 72. The data are presented as LSM (SE) change from baseline using ANCOVA with the last observation carried forward for missing data imputation (efficacy analysis set); *p < 0.05, **p < 0.01, ***p < 0.001 LSM change difference tirzepatide versus placebo. SF36v2 scores are norm based. The Van Hout value set was used to calculate the EQ-5D-5L Health State Index score. Only participants with a nonmissing baseline value and at least one nonmissing postbaseline value of the response variable were included in the analysis. ANCOVA analysis of covariance, EQ-5D-5L EuroQol 5 Dimension 5 Level, IWQOL-Lite-CT Impact of Weight on Quality of Life-Lite-Clinical Trials Version, LSM least squares mean, PBO placebo, SE standard error, SF-36v2 Short Form-36 Health Survey Version 2, TZP tirzepatide, VAS visual analog scale
Fig. 2.
Proportion of participants achieving clinically meaningful improvement in SF-36v2 physical functioning domain score at week 72. Efficacy Analysis Set. N number of participants in the population with baseline and post-baseline value at the specified time point, n number of participants achieving within-participant change from baseline ≥ 5.76 in SF-36v2 Acute Form Physical Functioning Domain Score, SF-36v2 Short Form-36 Health Survey Version 2. Within-participant clinically meaningful improvement in SF-36v2 Acute Form Physical Functioning Domain Score was achieved if the change from baseline value was equal to or greater than 5.76 (norm based). Anchor-based and distribution-based approaches were employed to determine the clinically meaningful within-patient change for the SF-36v2 physical functioning domain score, which indicated that an increase of 5.76 points was a reasonable estimate for improvement
Treatment with tirzepatide 10 mg and 15 mg was associated with significantly improved IWQOL-Lite-CT total, Psychosocial Composite, Physical Function Composite, and Physical Composite scores compared with placebo (all p < 0.001; Fig. 1b). EQ-5D-5L Health State Index (UK) score improvements with tirzepatide 10 or 15 mg were not significantly different to those with placebo (LSM (SE) change from baseline to week 72- tirzepatide 10 mg (n = 281): 0.03 (0.01); tirzepatide 15 mg (n = 265): 0.04 (0.01); placebo (n = 270): 0.02 (0.01)). However, LSM (SE) change from baseline to week 72 for EQ-VAS scores were significantly higher for the tirzepatide groups compared with placebo (tirzepatide 10 mg (n = 281): 8.7 (0.7); tirzepatide 15 mg (n = 266): 8.8 (0.7); placebo (n = 270): 3.4 (0.7)), p < 0.001 for both; Fig. 1c).
Table 1 presents data on the proportion of participants reporting limitations in physical activity at week 72. A numerically greater proportion of participants in the tirzepatide 10 mg group and 15 mg group (60%) reported no limitations in physical activity at week 72, relative to placebo (47%).
Table 1.
Shift table summary of PGIS from baseline to week 72
| Treatment | Response group at baseline | Response group at week 72 | ||||||
|---|---|---|---|---|---|---|---|---|
| Not at all limited, n (%) | A little limited, n (%) | Moderately limited, n (%) | Very much limited, n (%) | Extremely limited, n (%) | Missing, n (%) | Total, n (%) | ||
| Placebo | Not at all limited, n (%) | 94 (29.8) | 27 (8.6) | 2 (0.6) | 2 (0.6) | 0 | 25 (7.9) | 150 (47.6) |
| (n = 315) | A little limited, n (%) | 38 (12.1) | 27 (8.6) | 14 (4.4) | 1 (0.3) | 1 (0.3) | 14 (4.4) | 95 (30.2) |
| Moderately limited, n (%) | 11 (3.5) | 12 (3.8) | 10 (3.2) | 2 (0.6) | 1 (0.3) | 10 (3.2) | 46 (14.6) | |
| Very much limited, n (%) | 4 (1.3) | 4 (1.3) | 5 (1.6) | 5 (1.6) | 0 | 3 (1.0) | 21 (6.7) | |
| Extremely limited, n (%) | 1 (0.3) | 1 (0.3) | 0 | 1 (0.3) | 0 | 0 | 3 (1.0) | |
| Missing, n (%) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Total, n (%) | 148 (47.0) | 71 (22.5) | 31 (9.8) | 11 (3.5) | 2 (0.6) | 52 (16.5) | 315 (100.0) | |
| Tirzepatide 10 mg | Not at all limited, n (%) | 120 (38.5) | 13 (4.2) | 2 (0.6) | 4 (1.3) | 1 (0.3) | 10 (3.2) | 150 (48.1) |
| (n = 312) | A little limited, n (%) | 42 (13.5) | 26 (8.3) | 3 (1.0) | 3 (1.0) | 1 (0.3) | 16 (5.1) | 91 (29.2) |
| Moderately limited, n (%) | 18 (5.8) | 20 (6.4) | 5 (1.6) | 1 (0.3) | 0 | 4 (1.3) | 48 (15.4) | |
| Very much limited, n (%) | 4 (1.3) | 7 (2.2) | 2 (0.6) | 3 (1.0) | 0 | 1 (0.3) | 17 (5.4) | |
| Extremely limited, n (%) | 2 (0.6) | 0 | 1 (0.3) | 1 (0.3) | 0 | 2 (0.6) | 6 (1.9) | |
| Missing, n (%) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Total, n (%) | 186 (59.6) | 66 (21.2) | 13 (4.2) | 12 (3.8) | 2 (0.6) | 33 (10.6) | 312 (100.0) | |
| Tirzepatide 15 mg | Not at all limited, n (%) | 109 (35.0) | 14 (4.5) | 1 (0.3) | 0 | 0 | 24 (7.7) | 148 (47.6) |
| (n = 311) | A little limited, n (%) | 46 (14.8) | 26 (8.4) | 3 (1.0) | 2 (0.6) | 0 | 11 (3.5) | 88 (28.3) |
| Moderately limited, n (%) | 23 (7.4) | 12 (3.9) | 7 (2.3) | 1 (0.3) | 0 | 4 (1.3) | 47 (15.1) | |
| Very much limited, n (%) | 6 (1.9) | 1 (0.3) | 4 (1.3) | 3 (1.0) | 1 (0.3) | 7 (2.3) | 22 (7.1) | |
| Extremely limited, n (%) | 2 (0.6) | 1 (0.3) | 1 (0.3) | 1 (0.3) | 0 | 1 (0.3) | 6 (1.9) | |
| Missing, n (%) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Total, n (%) | 186 (59.8) | 54 (17.4) | 16 (5.1) | 7 (2.3) | 1 (0.3) | 47 (15.1) | 311 (100.0) | |
Efficacy Analysis Set; off-treatment data excluded
N number of participants in the population in the specified treatment group, n number of participants in the specified category, PGIS Patient Global Impression of Status for Physical Activity
Post Hoc Analyses in Tirzepatide-Treated Participants
Weight Reduction with Tirzepatide and Its Impact on HRQoL
Mean changes in SF-36v2, IWQOL-Lite-CT, and EQ-5D-5L scores from baseline to week 72 based on weight reduction targets are summarized in Table 2. All outcomes showed numerical improvements from baseline to week 72 across the weight reduction target groups (≥ 5%, ≥ 10%, ≥ 15%, ≥ 20%, ≥ 25%, and ≥ 30%). Bodyweight reductio n < 5% was associated with no or minimal improvements in outcomes.
Table 2.
Mean change in patient-reported outcomes by bodyweight target achieved and baseline PGIS category from baseline to week 72 among tirzepatide-treated participants
| HRQoL score, mean (SD) | Weight target achieved | Baseline PGIS category | |||||||
|---|---|---|---|---|---|---|---|---|---|
| < 5% | ≥ 5% | ≥ 10% | ≥ 15% | ≥ 20% | ≥ 25% | ≥ 30% | Without limitations | With limitations | |
| SF-36v2 | n = 36 | n = 515 | n = 423 | n = 291 | n = 172 | n = 87 | n = 42 | n = 423 | n = 128 |
| Mental component score | 1.1 (7.8) | 1.0 (8.1) | 1.1 (8.3) | 1.8 (8.5) | 2.1 (8.8) | 1.4 (8.6) | 2.2 (10.6) | 0.2 (6.8) | 3.8 (10.8) |
| Physical component score | −0.9 (5.9) | 3.8 (7.2) | 4.0 (7.3) | 4.8 (7.6) | 5.0 (7.8) | 5.2 (8.0) | 6.3 (9.6) | 2.3 (6.3) | 7.6 (8.4) |
| Domain scores (norm based) | |||||||||
| Physical functioning | −0.0 (7.6) | 3.8 (7.7) | 4.0 (7.7) | 4.7 (7.9) | 4.6 (8.2) | 4.7 (8.1) | 5.1 (9.5) | 2.3 (6.9) | 7.7 (9.0) |
| Role-physical | −0.2 (7.4) | 2.7 (8.2) | 2.8 (8.3) | 3.5 (8.8) | 3.8 (8.2) | 3.8 (8.1) | 4.1 (9.9) | 1.2 (7.1) | 7.0 (9.8) |
| Bodily pain | −0.1 (7.9) | 2.6 (9.1) | 2.6 (9.5) | 3.5 (9.7) | 4.1 (9.7) | 3.5 (10.6) | 5.3 (12.4) | 1.3 (8.5) | 5.8 (9.9) |
| General health | −0.8 (8.7) | 4.7 (8.2) | 4.9 (8.2) | 5.7 (8.7) | 5.8 (9.2) | 6.8 (9.5) | 8.7 (10.0) | 3.2 (7.7) | 8.1 (9.0) |
| Vitality | −1.1 (8.1) | 2.2 (8.5) | 2.6 (8.5) | 3.3 (9.1) | 3.7 (9.0) | 4.1 (9.8) | 5.2 (11.0) | 0.7 (7.3) | 6.1 (10.7) |
| Social functioning | −0.4 (8.1) | 1.3 (8.2) | 1.4 (8.6) | 2.0 (8.4) | 2.1 (8.3) | 0.9 (7.8) | 1.6 (9.7) | 0.3 (7.4) | 3.9 (10.1) |
| Role-emotional | 1.4 (8.6) | 2.0 (9.4) | 2.0 (9.4) | 3.1 (10.0) | 3.2 (10.1) | 1.9 (8.9) | 2.9 (9.9) | 0.8 (7.9) | 5.9 (12.3) |
| Mental health | 1.7 (6.8) | 1.6 (7.7) | 1.8 (8.0) | 2.3 (8.1) | 2.6 (8.5) | 2.9 (8.5) | 3.3 (10.4) | 0.8 (6.8) | 4.4 (9.6) |
| IWQOL-Lite-CT | n = 36 | n = 515 | n = 422 | n = 290 | n = 170 | n = 85 | n = 41 | n = 423 | n = 128 |
| Total score | 1.5 (8.0) | 14.7 (18.1) | 15.4 (18.6) | 18.5 (19.9) | 20.1 (21.0) | 19.8 (20.6) | 23.0 (20.2) | 10.2 (15.0) | 25.7 (21.4) |
| Physical function composite score | 0.1 (14.2) | 15.7 (22.3) | 16.4 (22.7) | 19.6 (24.2) | 21.4 (24.9) | 22.1 (26.9) | 26.3 (28.3) | 10.8 (17.9) | 27.4 (29.2) |
| Physical composite score | −0.1 (12.0) | 15.0 (20.8) | 15.8 (21.1) | 19.0 (22.3) | 20.8 (22.9) | 20.8 (24.0) | 25.1 (25.1) | 10.1 (16.7) | 27.0 (26.6) |
| Psychosocial composite score | 2.4 (9.5) | 14.5 (19.4) | 15.2 (20.0) | 18.3 (21.5) | 19.7 (22.8) | 19.3 (22.1) | 22.0 (21.1) | 10.3 (16.8) | 25.1 (22.0) |
| EQ-5D-5L | n = 36 | n = 510 | n = 418 | n = 287 | n = 169 | n = 85 | n = 41 | n = 417 | n = 129 |
| EQ-5D-5L health state index | − 0.0 (0.2) | 0.0 (0.2) | 0.0 (0.2) | 0.1 (0.2) | 0.1 (0.2) | 0.1 (0.2) | 0.1 (0.2) | 0.0 (0.2) | 0.1 (0.2) |
| EQ VAS score | n = 36 | n = 511 | n = 419 | n = 288 | n = 170 | n = 86 | n = 42 | n = 418 | n = 129 |
| 2.6 (12.5) | 9.7 (15.4) | 10.6 (15.4) | 12.3 (15.8) | 12.7 (16.5) | 12.7 (15.6) | 12.5 (16.0) | 7.6 (13.2) | 14.8 (19.9) | |
Efficacy Analysis Set—tirzepatide-treated participants (all doses pooled). Participants with a nonmissing baseline and at least one nonmissing post-baseline value are included in the analysis
ED-5D-5L EuroQol 5 Dimension 5 Level, IWQOL-Lite-CT Impact of Weight on Quality of Life-Lite Clinical Trials, LOCF last observation carried forward, n number of participants with nonmissing baseline and at least one nonmissing post-baseline value, PGIS Patient Global Impression Status, SD standard deviation, SF-36v2 Short Form-36 Health Survey version 2
For SF-36v2, the general health, mental health, role-physical, and vitality domain scores and PCS score improved in an increasing trend across the weight reduction target groups (≥ 5 to ≥ 30%). For IWQOL-Lite-CT, numerical improvements by weight reduction targets were observed for all composite scores and the total score. Participants achieving greater bodyweight reductions showed greater improvements in the EQ-5D-5L Health State Index (UK) scores. A similar pattern was noted for the EQ-VAS scores, with only slight variations in improvements among the ≥ 15%, ≥ 20%, ≥ 25%, and ≥ 30% weight reduction target groups. Supplementary Table S1 presents baseline scores for all HRQoL outcomes by weight reduction targets.
Changes in HRQoL Based on Limitations in Physical Functioning
Participants treated with tirzepatide 10 or 15 mg reporting limitations in physical functioning at baseline showed numerically greater mean change from baseline in all SF-36v2 and IWQOL-Lite-CT domains and the EQ-5D-5L Health State Index (UK) and EQ VAS scores, at week 72, compared with those without limitations at baseline (Table 2).
Discussion
In the SURMOUNT-2 clinical trial, adults with a BMI of 27 kg/m2 or higher and with T2D who received 10 or 15 mg tirzepatide for 72 weeks demonstrated significantly greater improvements in both self-reported physical and psychosocial aspects of HRQoL and physical functioning, relative to placebo. Significant improvements were observed with at least one dose of tirzepatide compared with placebo in the SF-36v2 PCS score, SF-36v2 physical functioning, bodily pain, general health, vitality, and social functioning domain scores, all IWQOL-Lite-CT scores, and the EQ VAS score.
Our findings concur with previous research demonstrating the association of tirzepatide use in individuals with obesity or T2D with improvements in HRQoL. Results from the SURMOUNT-1 trial showed that treatment with tirzepatide (10 or 15 mg) was associated with greater improvements in the SF-36v2 physical functioning scores from baseline to week 72, compared with placebo, among participants with obesity without T2D [11, 33]. Additionally, the SURPASS-2 trial that evaluated the efficacy of tirzepatide (5, 10, and 15 mg) as compared with semaglutide (1 mg) among participants with T2D demonstrated that tirzepatide (15 mg) treatment was associated with significantly greater improvement in IWQOL-Lite-CT scores compared with semaglutide (all p < 0.05) [34]. The SURPASS-6 trial assessed tirzepatide as an alternative to insulin lispro in poorly controlled basal insulin-treated adults with T2D. Results indicated that tirzepatide was associated with significantly improved SF-36v2 component and domain scores versus insulin lispro (all p < 0.05) [35, 36].
Previous studies using non-disease state-specific and obesity‐specific PRO measures have demonstrated a positive association between better HRQoL and weight reduction [19, 37, 38]. However, a recurrent pattern observed across numerous studies is that this association is more consistent for physical aspects of HRQoL than mental aspects [38–40]. Our findings echo this pattern, with improvements observed across all domains but not always reaching statistical significance for mental aspects of HRQoL outcomes. Notably, we also saw numerically greater improvements in self-reported HRQoL outcomes, particularly physical functioning, among participants who achieved greater magnitudes of bodyweight reduction. Our findings suggest that these improvements may be an effect of weight reduction rather than an independent effect of tirzepatide treatment.
Obesity and T2D have been associated with lower levels of physical activity and physical function [18, 41]. Despite its significance in obesity management, implementing intensive lifestyle intervention may prove challenging for people with physical functioning limitations [42]. In our study, participants who reported limitations in physical function at baseline showed numerically greater improvements in HRQoL versus participants who did not report limitations. These results highlight the potential benefits of tirzepatide-induced weight reduction for this population. Further studies focusing on individuals with more severe baseline physical function limitations could offer additional insights into the applicability of these findings in a real-world setting.
In recent years, there has been growing recognition of a patient-centered approach to managing T2D and obesity, both of which are chronic conditions that often coexist and are associated with significant morbidity and mortality [43–45]. With the increasing emphasis on establishing goals of care and the expanding array of available treatment options, assessing the impact of a specific treatment on patients’ QoL becomes increasingly essential [46]. Incorporating PROs in clinical studies can help identify barriers to treatment adherence and guide clinicians in developing a treatment plan that fits the personal preferences and goals of an individual, consequently leading to improved clinical outcomes [47, 48]. Improvements in self-reported HRQoL outcomes in the SURMOUNT-2 trial demonstrate that weight reduction among participants receiving tirzepatide may translate into benefits extending beyond the conventional clinical outcomes.
Limitations of this study included the predominantly white demographic, which may potentially limit the generalizability of the results to more diverse populations. Furthermore, the post hoc analyses were descriptive in nature and lacked corresponding data for the placebo arm because there were limited or no data for the higher weight reduction targets in the placebo arm. Additionally, the 5 mg tirzepatide dose, an approved dose for the treatment of T2D that produced substantial reductions in bodyweight, was not evaluated in the SURMOUNT-2 trial.
Conclusions
In the SURMOUNT-2 clinical trial, self-reported HRQoL outcomes significantly improved in terms of physical and psychosocial aspects of functioning in participants with obesity and T2D who were treated with tirzepatide compared with placebo. In post hoc analyses, improvements in self-reported HRQoL outcomes were numerically greater among participants achieving greater bodyweight reduction and among those who reported limitations in physical function at baseline.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
The authors thank the participants and study investigators of the SURMOUNT-2 clinical trial. The authors thank Cathy Xie for providing statistical peer review support.
Medical Writing, Editorial, and Other Assistance
The authors thank Mythili Ananth and Richa Kapoor, employees of Eli Lilly Services India Pvt. Ltd., for providing medical writing support, which was funded by Eli Lilly and Company.
Authorship
All named authors meet the International Committee of Medical Journal Editors criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Author Contributions
Conception: Theresa Hunter Gibble Design: Theresa Hunter Gibble, Dachuang Cao, and Jiat Ling Poon Acquisition of data: Dachuang Cao and Xiaotian Michelle Zhang Analysis of data: Dachuang Cao and Neena Agarwal Xavier, Theresa Hunter Gibble, Dachuang Cao, Xiaotian Michelle Zhang, Neena Agarwal Xavier, Jiat Ling Poon, and Angela Fitch were involved in the interpretation of the study results and provided critical revisions during the development of this manuscript.
Funding
The study and all support for the manuscript, including the journal’s Rapid Service Fee, were funded by Eli Lilly and Company, Indianapolis, USA.
Data Availability and Sharing Statement
Eli Lilly and Company provides access to all individual participant data collected during the trial after anonymization, except for pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the USA and European Union and after primary publication acceptance, whichever is later. No expiration date for data requests is currently set once data have been made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data-sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, and blank or annotated case report forms, will be provided in a secure data-sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.
Declarations
Conflicts of Interest
Theresa Hunter Gibble, Dachuang Cao, Xiaotian Michelle Zhang, Neena Agarwal Xavier and Jiat Ling Poon are employees and shareholders of Eli Lilly and Company. Angela Fitch reports personal fees from Eli Lilly and Company, Novo Nordisk, Rhythm, Currax, Neurobo, Nestle, Jenny Craig, Sidekick, Abbvie, Carmot, and Vivus and non-financial support from Seca during the conduct of the study.
Ethical Approval
The study protocol was approved by local institutional review boards and adhered to the principles outlined in the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. All participants provided written informed consent prior to the study.
Footnotes
Prior Presentation: A portion of the results included in this manuscript was previously presented as a poster presentation at the 33rd Annual Meeting and Clinical Congress of the American Association of Clinical Endocrinology, held between 9 and 11 May 2024 in New Orleans. The corresponding abstract was published in Endocrine Practice (no. 1704957 Tirzepatide Improves Health-Related Quality of Life in Participants with Obesity or Overweight and Type 2 Diabetes: Results from Phase 3 SURMOUNT-2 Trial. Hunter, Theresa, et al. Endocrine Practice, Volume 30, Issue 5, S70. 10.1016/j.eprac.2024.03.263).
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Eli Lilly and Company provides access to all individual participant data collected during the trial after anonymization, except for pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the USA and European Union and after primary publication acceptance, whichever is later. No expiration date for data requests is currently set once data have been made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data-sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, and blank or annotated case report forms, will be provided in a secure data-sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.