Language

English

Publication Date

4-21-2026

Journal

Journal of the American College of Cardiology

DOI

10.1016/j.jacc.2026.01.013

PMID

41811272

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.

Keywords

Humans, Obesity, Cardiovascular Diseases, Anti-Obesity Agents, Clinical Trials as Topic, Glucagon-Like Peptide-1 Receptor Agonists, GLP-1 receptor agonist, antiobesity medications, cardiovascular outcomes trial, heart failure, obesity, safety

Published Open-Access

yes

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