Cardiovascular Effects of GLP-1 Receptor Agonists in Non-Diabetic Adults With Obesity: A Systematic Literature Review

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with obesity. GLP-1 receptor agonists, initially developed for glycemic control in diabetes, are now approved for weight loss in non-diabetic populations. Recent clinical trials suggest these agents may also offer direct cardiovascular benefits. Objective: This literature review aims to evaluate the cardiovascular effects of GLP-1 receptor agonists, specifically semaglutide, liraglutide, and tirzepatide, in non-diabetic adults with overweight or obesity. Methods: A systematic search was conducted in January 2025 using PubMed as the primary database, supplemented by Google Scholar and Embase. Clinical trials were selected based on predefined inclusion criteria, requiring cardiovascular outcomes beyond weight loss in non-diabetic populations. Fifteen eligible studies were analyzed. Results: GLP-1 agonists demonstrated improvements in several cardiovascular domains, including reductions in NT-proBNP, CRP, and structural cardiac abnormalities, as well as enhanced functional status measured by NYHA class or KCCQ-CSS. Semaglutide showed the most consistent benefits across endpoints. A strong association was observed between greater weight loss (≥10%) and NT-proBNP reduction, suggesting a potential mechanistic link. Conclusion: GLP-1 receptor agonists, especially semaglutide, show promise as cardioprotective agents in non-diabetic adults with obesity. However, more dedicated trials with longer follow-up are needed to validate these benefits and optimize patient selection.