Doxorubicin-Induced Cardiotoxicity and the Emerging Role of SGLT2 Inhibitors: From Glycemic Control to Cardio-Oncology

Abstract

Cancer remains the second leading cause of death worldwide. Doxorubicin (DOX) is a cornerstone of hematologic malignancy treatment, but it is limited by its dose-dependent cardiotoxicity, leading to systolic and diastolic cardiac dysfunction and, ultimately, dilated hypokinetic cardiomyopathy. Cardio-oncology has emerged as a subspecialty addressing cardiovascular complications in cancer patients, highlighting preventive and therapeutic strategies to reduce cancer therapy-related cardiac dysfunction (CTRCD). Current approaches, including beta-blockers, renin–angiotensin system (RAS) inhibitors, and statins, offer partial cardioprotection. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially developed for type 2 diabetes mellitus (T2DM), demonstrate pleiotropic cardioprotective effects beyond glycemic control, including reduced oxidative stress, inflammation, and myocardial remodeling. This review explores the interplay between anthracycline therapy, particularly DOX, and cardiotoxicity while evaluating SGLT2 inhibitors as novel agents in cardio-oncology. Preclinical studies suggest SGLT2 inhibitors attenuate CTRCD by preserving mitochondrial function and inhibiting apoptosis, while clinical trials highlight their efficacy in reducing heart failure (HF) hospitalizations and cardiovascular (CV) mortality. Integrating SGLT2 inhibitors into cardio-oncology protocols could revolutionize the management of CTRCD, enhancing patient outcomes in oncology and cardiovascular care. Considering the emerging evidence, SGLT2 inhibitors may provide significant benefits to patients undergoing anthracycline therapy, particularly those with elevated cardiovascular risk profiles. We recommend that future prospective, large-scale clinical trials further evaluate the efficacy and safety of these agents as cardioprotective therapy to optimize individualized treatment strategies.