GLP-1 receptor agonists may reduce arrhythmia risk through effects on cell death, metabolism, inflammation, autophagy, ion balance, and autonomic signaling.
Evidence
This mechanistic review synthesizes preclinical evidence and large-scale clinical trial findings on and arrhythmia risk.
Caveat
The antiarrhythmic mechanisms remain incompletely understood, and the review synthesizes rather than directly tests these pathways.
Simplified
Glucagon-like peptide-1 receptor agonists () are a novel class of glucose-lowering agents that offer benefits beyond glycemic control and weight loss and are increasingly recognized for their cardioprotective benefits, including protective effects against hypertension, heart failure, myocardial infarction, and . Notably, GLP-1RAs have demonstrated a significant capacity to reduce arrhythmia risk not only in animal models but also in large-scale clinical trials. However, the antiarrhythmic mechanisms of GLP-1RAs remain incompletely understood. This mechanistic review synthesizes current preclinical and clinical evidence to delineate the key pathways through which GLP-1RAs may exert their antiarrhythmic effects. The primary mechanisms discussed include the attenuation of cardiomyocyte death, improvement of myocardial metabolism, and inhibition of the inflammatory response. Additional mechanisms, such as the promotion of autophagy, maintenance of ion homeostasis in cardiomyocytes, and modulation of the autonomic nervous system, are also examined. By clarifying these mechanisms, this review aims to offer novel therapeutic strategies for arrhythmia prevention, especially in the high-risk population with cardiometabolic diseases.
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