J Am Coll Cardiol. 2026 Mar 4:S0735-1097(26)00076-8. doi: 10.1016/j.jacc.2026.01.013. Online ahead of print.
ABSTRACT
The prevalence of obesity has reached pandemic proportions and is having enormous public health effects. Obesity increases the risk of type 2 diabetes, hypertension, chronic kidney disease, and cardiovascular (CV) disease including coronary artery disease, heart failure, atrial fibrillation, and stroke. Although initial randomized clinical trials of weight-loss strategies through diet and exercise or early medical therapies did not lead to improved CV outcomes, more recent trials using glucagon-like peptide-1 (GLP-1) receptor agonists in individuals with obesity have demonstrated CV benefits. At present, there are multiple cardiovascular outcome trials (CVOTs) of novel GLP-1 receptor agonists and investigational products targeting multiple hormonal pathways planned or underway. However, the optimal design features of CVOTs testing novel obesity medications may need to evolve. In this commentary, we discuss regulatory aspects and study design considerations of CVOTs for obesity medications in the context of previous and ongoing clinical trials and the future of CVOTs targeting obesity. We also propose 5 principles to help guide next-generation cardio-kidney-metabolic outcome trials.
PMID:41811272 | DOI:10.1016/j.jacc.2026.01.013