Tirzepatide achieves 7.2% greater weight loss than semaglutide in obesity patients meeting Japan's criteria

The global prevalence of obesity disease continues to rise, posing significant public health challenges due to its association with numerous cardiometabolic comorbidities like hypertension and dyslipidemia. While lifestyle interventions are foundational, pharmacotherapy is often necessary for sustained weight management. Current standard-of-care treatments, including GLP-1 receptor agonists like semaglutide, have demonstrated efficacy, but there remains a need for even more potent options. Tirzepatide, a dual GLP-1R and GIPR agonist, offers a novel mechanism that may provide superior weight loss and metabolic improvements, particularly for populations with specific diagnostic criteria, such as those defined by the Japan Society for the Study of Obesity.

This was a subpopulation analysis of the global SURMOUNT-5 trial (NCT05822830), focusing on 383 participants who met Japan's national insurance criteria for obesity disease. These criteria included individuals with hypertension or dyslipidemia and a BMI 27-35 kg/m2 with ≥2 obesity-related health disorders (ORHDs), or a BMI ≥35 kg/m2 with ≥1 ORHD. Participants were randomized to receive either tirzepatide 15 mg (or maximum tolerated dose) or semaglutide 2.4 mg (or maximum tolerated dose) for 72 weeks. Primary endpoints included percent change in body weight, with secondary outcomes assessing changes in waist circumference, BMI, and cardiometabolic factors. Between-group comparisons utilized analysis of covariance, while changes over time were assessed with a mixed model for repeated measures.

Of the 750 participants in the overall SURMOUNT-5 trial, 383 met the specific Japanese obesity criteria and were included in this sub-analysis (n=190 for tirzepatide; n=193 for semaglutide). At Week 72, the least-squares mean (LSM) percent change in body weight was significantly greater for tirzepatide compared to semaglutide. Participants receiving tirzepatide achieved an LSM body weight reduction of -20.1% (SE 0.76%), while those on semaglutide achieved -12.9% (0.74%). This resulted in an LSM difference of -7.2% (95% CI = -9.3 to -5.1; p <.001).