Tirzepatide cuts predicted 10-year cardiovascular disease risk by 2.8% in Japanese adults with obesity

Managing obesity disease is critical for mitigating cardiovascular disease (CVD) risk, especially in populations like Japan where specific diagnostic criteria exist. Current lifestyle interventions often fall short in achieving sustained weight loss and comprehensive cardiometabolic improvements. This creates a significant gap for pharmacotherapeutic agents that can not only reduce body weight but also directly impact long-term CVD risk factors. Tirzepatide, a dual GLP-1R and GIPR agonist, has demonstrated potent effects on weight loss and various cardiometabolic parameters, making it a promising candidate for primary CVD prevention in this vulnerable population.

This post hoc analysis of the phase 3 SURMOUNT-J trial enrolled 186 Japanese adults with obesity disease (JASSO criteria) but no diabetes or prior CVD. Participants were randomized to once-weekly tirzepatide 10 mg, tirzepatide 15 mg, or placebo for 72 weeks. The primary endpoint was the change in predicted 10-year CVD risk from baseline to Week 72, calculated using Framingham risk equations. The study also projected the number of potentially preventable CVD events using national statistics and the Medical Data Vision database to estimate population-level impact.

At baseline, the mean predicted 10-year CVD risk was 12.6% across all participants. Tirzepatide treatment significantly reduced this predicted risk by Week 72. > The 10 mg dose of tirzepatide led to a mean absolute reduction of 2.8% (95% CI: -3.7%, -1.9%) from baseline, while the 15 mg dose showed a 2.5% reduction (95% CI: -3.4%, -1.6%). In stark contrast, the placebo group experienced a mean increase of 2.0% (95% CI: 1.1%, 2.9%) in predicted risk. Model-derived hazard ratios for tirzepatide were 0.65 (10 mg) and 0.68 (15 mg) versus placebo, both with p < 0.001. These risk reductions were evident as early as Week 8 and sustained throughout the 72-week treatment period. Extrapolating to approximately 5.1 million eligible individuals in Japan, the model projected 123,000 potentially preventable CVD events over 10 years with tirzepatide (10 mg), compared to an estimated increase of 88,000 events with placebo.