The dual role of SGLT2 inhibitors: glycemic control and cardioprotection in anthracycline-treated cancer patients.

Abstract

Anthracyclines are vital chemotherapy drugs for treating various cancers, including solid tumors and blood cancers; however, they cause dose-dependent cardiotoxicity, manifesting as cardiomyopathy, arrhythmias, and heart failure (HF). Cardiotoxicity, driven by oxidative stress, mitochondrial dysfunction, and other mechanisms, limits its use and affects long-term patient outcomes. Meanwhile, sodium-glucose co-transporter-2 (SGLT2) inhibitors, originally developed for type 2 diabetes, offer cardiovascular benefits beyond glucose control, such as reduced HF hospitalization and mortality. These benefits stem from improved myocardial energetics, reduced fibrosis, and improved regulation of cardiac ion homeostasis. Experimental studies, including animal models, have shown that SGLT2 inhibitors, such as empagliflozin, preserve cardiac function and reduce inflammation in anthracycline-induced cardiotoxicity. Clinical data, although limited to small retrospective studies, suggest lower mortality and fewer cardiovascular events in anthracycline-treated cancer patients using SGLT2 inhibitors. However, variability in the study design highlights the need for a systematic evaluation. This systematic review aimed to critically assess the cardiovascular outcomes associated with SGLT2 inhibitor use in cancer patients treated with anthracyclines, evaluating their dual role in glycemic control and cardioprotection, and to identify evidence gaps to inform therapeutic strategies for optimizing long-term cardiovascular health in this vulnerable population.