Lifetime Risk from Obesity, and benefits of anti-obesity pharmacotherapy and global impact: A Multinational pooled analysis and modelling Study

The rising global prevalence of obesity poses a major threat to cardiovascular health, yet the lifetime cardiovascular disease (CVD) risks and the potential global impact of new anti-obesity medications are poorly quantified. Here, through a pooled analysis of individual-level data from 135,261 participants across seven international cohorts, we quantify the lifetime risk of CVD associated with obesity and model the benefits of semaglutide therapy. We show that obesity is associated with a substantially increased lifetime CVD risk (65.6%, 95% CI 64.4–66.8% at age 50) compared to normal weight (56.3%, 95% CI 55.4–57.3%). For individuals eligible for semaglutide, we project that initiating treatment at age 50 could extend CVD-free survival by 2.21 years (95% CI 1.07–3.20), a benefit that diminishes with increasing age. Extrapolating these findings using nationally representative data from 99 countries, we reveal wide variation in treatment eligibility and project that widespread semaglutide implementation could prevent millions of CVD events, with the largest absolute numbers in the United States (3.32 million) and China (1.85 million). Our findings demonstrate that early anti-obesity pharmacotherapy offers substantial lifetime benefits and underscore the urgent need for equitable, evidence-based policies to mitigate the global burden of obesity-related CVD.