Key result
Tirzepatide drives ~7% greater body weight loss than semaglutide at 72 weeks.
Why the study?
The efficacy and safety of tirzepatide versus semaglutide remained to be evaluated in individuals eligible for obesity disease pharmacotherapy under Japan's national insurance criteria.
Does tirzepatide improve weight loss compared to semaglutide in individuals with obesity disease?
RCT (n=383)
Yes
Does tirzepatide improve weight loss compared to semaglutide in individuals with obesity disease?
Tirzepatide provides superior weight loss, BMI reduction, and waist circumference reduction compared to semaglutide in patients meeting Japanese criteria for obesity disease.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The SURMOUNT-5 head-to-head results demonstrated tirzepatide led to greater weight reduction compared to semaglutide, providing further evidence to support tirzepatide as an effective option for obesity management.”
“In the SURMOUNT-5 trial, Zepbound demonstrated a significantly higher magnitude of weight reduction compared to Wegovy across all comparisons.”
“We have learned over the past 20-odd years that in order to overcome plateau phenomenon in obesity, if you can add mechanisms that are completely different together, you can often get additional weight loss. And that's exactly what the trial shows.”
May support tirzepatide preference for weight loss under national criteria; leaves open generalizability beyond this subpopulation.
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/m2 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/m2 and ≥2 obesity-related health disorders (ORHDs), or BMI ≥35 kg/m2 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], n = 190; semaglutide 2.4 mg or MTD, n = 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; p <.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
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Kitamoto et al. (2026) conducted an RCT in Obesity disease (n=383). Tirzepatide vs. Semaglutide 2.4 mg or maximum tolerated dose was evaluated on Percent change in body weight from baseline to Week 72 (MD -7.2, 95% CI -9.3 to -5.1, p=<.001). Tirzepatide resulted in a significantly greater percent reduction in body weight compared with semaglutide at 72 weeks (-20.1% vs -12.9%; MD -7.2, 95% CI -9.3 to -5.1; P<0.001).
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