Abstract

Obesity is an independent driver of cardiovascular disease (CVD), mediated through adverse haemodynamic loading, insulin resistance, systemic inflammation, endothelial dysfunction and prothrombotic pathways. Contemporary obesity therapies show cardiovascular (CV) benefits beyond improvements in traditional risk factors. Across large CV outcome trials, glucagon-like peptide 1 receptor agonists consistently reduce three-point major adverse CV events (MACE) in patients with overweight, obesity and established CVD with and without diabetes. In obesity-related heart failure of preserved ejection fraction, semaglutide and tirzepatide improve symptoms and functional capacity and reduce worsening heart failure events, while effects on CV mortality remain uncertain. In contrast, evidence for metabolic bariatric surgery is dominated by large observational cohorts and meta-analyses, which are associated with durable weight loss and lower observed rates of MACE, heart failure and all-cause mortality compared with non-surgical care, though causal inference is constrained by residual confounding. Data support that sustained weight loss of at least 10% is more likely to translate into CVD event reduction, alongside other organ specific mechanisms that impact CV health independent from weight reduction. Obesity treatments offer a safe and effective method to lose weight with varying CV benefits, with current evidence still in early stages to establish robust clinical recommendations.