Potential Antiarrhythmic Mechanisms of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs)

Mar 30, 2026Drug design, development and therapy

Possible Heart Rhythm Benefits of Drugs That Activate Glucagon-Like Peptide-1 Receptors

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Abstract

Glucagon-like peptide-1 receptor agonists () may significantly reduce arrhythmia risk based on large-scale clinical trials.

GLP-1RAs provide cardioprotective benefits beyond lowering blood sugar and promoting weight loss.
Evidence suggests that GLP-1RAs may protect against conditions such as hypertension, heart failure, and myocardial infarction.
The mechanisms by which GLP-1RAs may reduce arrhythmia risk include reducing cardiomyocyte death and improving heart muscle metabolism.
GLP-1RAs are associated with inhibition of the inflammatory response and promotion of autophagy.
They may also help maintain ion balance in heart cells and modulate the autonomic nervous system.

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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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Potential Antiarrhythmic Mechanisms of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs)

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