The Effects of GLP-1 Agonists on Cardiac Structure and Function: A Systematic Review

Abstract

Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as a promising therapeutic class for addressing the metabolic and cardiovascular complications of obesity and type 2 diabetes mellitus (T2DM). Given the elevated risk of cardiovascular disease in these populations, our review systematically evaluates the long-term effects (>6 months) of GLP-1 receptor agonists on the cardiac structure, function, and major adverse cardiac events (MACE).

Methods: A literature search was conducted via PubMed for English-language human studies published in the past five years that investigated GLP-1 receptor agonist treatment on cardiac structure and/or function. From the 131 initial results, 15 studies met the inclusion criteria for full-text review. The reviewed studies encompassed diverse populations, including patients with T2DM, heart failure with a preserved ejection fraction, coronary artery disease, and obesity.

Results: Results on cardiac structure varied; some studies reported reductions in left ventricular mass and left atrial volume with GLP-1 receptor agonists treatment, while others showed no significant structural changes. Cardiac function outcomes, such as left ventricular ejection fraction and myocardial strain metrics, were largely unchanged, particularly in patients with T2DM. GLP-1 receptor agonists were associated with increased myocardial perfusion and decreased NT-proBNP and C-reactive protein (CRP), suggesting cardioprotective effects. However, heart rate elevation and potential arrhythmic risks were observed in some studies. Importantly, many studies demonstrated reductions in MACE and all-cause mortality with semaglutide, while results for liraglutide were more variable.

Discussion: GLP-agonists demonstrate a myriad of effects on cardiac function and cardiac structure, some have significant effects while others had none. Significantly, MACE was reduced in most of the semaglutide treatments leading to less cardiac dysfunction. Liraglutide did lead to some reduction in MACE but not consistently.

Conclusion: Semaglutide does demonstrate a promising approach especially in the reduction of MACE while liraglutide did not have the uniform benefits. Studies with different forms of GLP-1 agonists distributed to diverse populations are needed to evaluate individualized effects on metabolic disorders.