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.
Level 2 - randomized trial
Subgroup analysis of an individual randomized controlled trial
PubMed 42434924 · doi:10.1080/03007995.2026.2695047
What was done
This was a subpopulation analysis of the global SURMOUNT-5 randomized controlled trial (NCT05822830) comparing tirzepatide (15 mg or maximum tolerated dose) to semaglutide (2.4 mg or maximum tolerated dose) over 72 weeks. The analysis included 383 participants (out of 750 in the overall trial) who met Japan Society for the Study of Obesity criteria for obesity disease pharmacotherapy (BMI 27–35 kg/m² with hypertension or dyslipidemia plus ≥2 obesity-related health disorders, or BMI ≥35 kg/m² with ≥1 disorder). Outcomes included percent body weight change, categorical weight-loss targets, waist circumference, BMI, and adverse events evaluated with ANCOVA and mixed models for repeated measures.
What was found
At Week 72, tirzepatide (n = 190) resulted in a significantly greater least-squares mean percent reduction in body weight compared with semaglutide (n = 193): -20.1% (SE 0.76%) versus -12.9% (SE 0.74%), with a treatment difference of -7.2% (95% CI = -9.3% to -5.1%; p < .001). Significantly higher proportions achieved ≥10%, ≥15%, ≥20%, ≥25%, and ≥30% weight reduction with tirzepatide. Significant differences favoring tirzepatide were also observed for waist circumference (from Week 4) and BMI (from Week 12). Gastrointestinal symptoms were the most common adverse events in both groups.
Why it matters
This study shows that tirzepatide provides superior weight and anthropometric reductions compared to semaglutide when applying specific clinical criteria used for obesity pharmacotherapy coverage in Japan.
Limits
This is a secondary subpopulation analysis rather than an independently powered trial. The abstract does not provide exact numeric event rates for adverse events, specific response percentages for categorical weight loss targets, or cardiometabolic lab values, nor does it evaluate outcomes beyond 72 weeks.
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- contradicts Tirzepatide produces more weight loss per milligram than any other commercially available GLP-1 drug.