Tirzepatide compared with semaglutide in obesity disease: a subpopulation analysis applying Japan Society for the Study of Obesity criteria in the global SURMOUNT-5 trial.

OBJECTIVE: To evaluate the efficacy and safety of tirzepatide versus semaglutide in individuals eligible for pharmacotherapy for obesity disease under Japan's national insurance criteria, where obesity is defined as body mass index (BMI) ≥25 kg/m with excess adiposity. METHODS: This subpopulation analysis of the SURMOUNT-5 trial (NCT05822830) included participants meeting obesity disease criteria: hypertension or dyslipidemia with BMI 27-35 kg/m and ≥2 obesity-related health disorders (ORHDs), or BMI ≥35 kg/m with ≥1 ORHD. Outcomes were assessed from baseline to Week 72, including percent change in body weight, proportions achieving weight-loss thresholds, changes in waist circumference, BMI, cardiometabolic factors, and adverse events. Between-group comparisons used analysis of covariance. Changes over time were assessed with a mixed model for repeated measures. RESULTS: Of 750 participants, 383 met the criteria for obesity disease (tirzepatide 15 mg or maximum tolerated dose [MTD],  = 190; semaglutide 2.4 mg or MTD,  = 193). At Week 72, the least-squares mean (LSM) percent change in body weight was significantly greater for tirzepatide (-20.1% [SE 0.76%]) versus semaglutide (-12.9% [0.74%]), with an LSM difference of -7.2 (95% CI = -9.3 to -5.1;  <.001). More participants receiving tirzepatide achieved ≥10%, ≥15%, ≥20%, ≥25%, and ≥30% weight-loss targets. Reductions in waist circumference and BMI were significantly greater with tirzepatide, evident from Weeks 4 and 12, respectively, and maintained through Week 72. The safety profile was generally consistent with the overall SURMOUNT‑5 population, with gastrointestinal events most common. CONCLUSION: In this subpopulation analysis, tirzepatide was associated with greater reductions in weight, BMI, and waist circumference than semaglutide in individuals with obesity disease. STUDY REGISTRATION: ClinicalTrials.gov, NCT05822830.