Exploring the Pleiotropic Cardioprotective Effects of GLP-1 Receptor Agonists in Preventing Anthracycline-Induced Cardiotoxicity: A Theoretical Proposal for Future Research

TL;DR

This paper proposes that GLP-1 receptor agonists may protect the heart from chemotherapy-induced damage, offering a new area for research in cardio-oncology.

Contribution

The paper introduces a theoretical framework for using GLP-1 receptor agonists as a novel cardioprotective strategy against anthracycline-induced cardiotoxicity.

Findings

GLP-1 receptor agonists have pleiotropic effects that may counteract anthracycline-induced cardiotoxicity.

Current cardioprotective agents like dexrazoxane are limited, highlighting the need for new therapies like GLP-1 RAs.

Anti-inflammatory and antioxidant mechanisms of GLP-1 RAs could mitigate myocardial injury from chemotherapy.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to reduce morbidity and mortality associated with type II diabetes mellitus, and/or obesity, and/or cardiovascular disease in multiple clinical trials. Their efficacy in reversing cardiovascular disease and mitigating the risk of major adverse cardiac and vascular events has been well studied, with outcome trials consistently demonstrating benefits such as reduced systemic inflammation, improved endothelial function, and favorable metabolic effects. These pleiotropic actions have nearly innumerable potential applications, with a progressively growing interest in using GLP-1 RAs to mitigate increased cardiovascular disease risk secondary to other off-target pharmacologic agents. Given these effects, the potential to utilize GLP-1 RAs for prophylactic cardioprotection before, during, and/or after chemotherapy regimens is of great interest. These effects are thought to be mediated in part through anti-inflammatory and antioxidant mechanisms that counter inflammation and reactive oxygen species-driven myocardial injury central to anthracycline-induced cardiotoxicity (AIC). Anthracyclines, a widely used class of chemotherapeutics for various malignancies, are frequently associated with dose-dependent and often irreversible cardiotoxicity, leading to heart failure, reduced quality of life, and adverse long-term outcomes. For the past three decades, dexrazoxane has been the sole Food and Drug Administration-approved agent for cardioprotection in this setting. However, in the current era of novel therapies with multi-system benefits—such as GLP-1 RAs—we propose a theoretical framework exploring their potential role in mitigating AIC and underscore the need for further clinical investigation in this new arena in the field of cardio-oncology.

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