(3.09) Improvements in Physical Functioning Among Participants With Obesity With Limitations in Physical Function at Baseline: Results from SURMOUNT-1 and SURMOUNT-2 Trials

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. SURMOUNT-1 and -2 trials investigated efficacy of tirzepatide for weight reduction in participants without or with T2D, respectively. We assessed effect of tirzepatide treatment on physical function among SURMOUNT-1 and -2 participants who reported limitations in physical function at baseline.

Methods: SURMOUNT-1 and -2 participants with obesity (body mass index [BMI]≥30kg/m²), or overweight (BMI≥27kg/m²) with weight-related comorbidities, were randomized to placebo (PBO) or tirzepatide (SURMOUNT-1: 5/10/15mg; SURMOUNT-2: 10/15mg) for 72 weeks. Patient-reported outcomes questionnaires were completed at baseline, Week (Wk) 72: 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). Responses to Patient Global Impression of Status for Physical Activity item (“Please choose the response that best describes how your health limited your ability to perform physical activities during the past week”) were used to identify those with moderately, very, or extremely limited physical function at baseline. Mean scores and least squares mean (LSM) change differences (diff) in SF-36v2 Physical Functioning (PF) and IWQOL-Lite-CT Physical Function composite (PFc) scores from baseline to Wk72 were analyzed for PBO and tirzepatide groups (10mg and 15mg) using analysis of covariance with last observation carried forward for imputation of missing data.

Results: At baseline, 318 participants in SURMOUNT-1 (PBO: n=93; tirzepatide 10mg: n=123; tirzepatide 15mg: n=102) and 187 in SURMOUNT-2 (PBO: n=59; tirzepatide 10mg: n=64; tirzepatide 15mg: n=64) reported limitations in physical function. At baseline, mean SF‑36v2 PF scores did not differ between groups in both studies (range: 39.2–43.3). At Wk72, LSM change diff were significantly higher (better) for tirzepatide groups vs PBO (SURMOUNT-1: pooled tirzepatide 10/15mg=4.5; SURMOUNT-2: tirzepatide 10mg=4.2; tirzepatide 15mg=3.8; all p< 0.05). Mean IWQOL-Lite-CT PFc scores at baseline did not differ between groups in both studies (range: 38.1–44.5). LSM change diff were significantly higher (better) for tirzepatide groups vs PBO at Wk72 (SURMOUNT-1: tirzepatide 10mg=16.3; tirzepatide 15mg=16.4; SURMOUNT-2: tirzepatide 10mg=9.7; tirzepatide 15mg=11.8; all p< 0.05).

Discussion/Conclusion: Tirzepatide showed improvement vs PBO in physical function at 72 weeks among participants with obesity or overweight with or without T2D who reported physical function limitations at baseline.