Cardioprotective effect of diabetic medication on cancer patients undergoing proven cardiotoxic chemotherapy: a systematic review and meta-analysis

Abstract

Multiple chemotherapeutic agents, such as anthracyclines, have recently shown a fatal potential for cardiotoxic effects in their patients. However, their efficacy is often hindered by their harmful adverse effects, mostly cardiotoxicity. DM medications such as metformin, SGLT-2 inhibitors, and GLP-1 receptor agonists have exhibited promising cardioprotective properties in rat clinical trials. We conducted our study to investigate the observational association between diabetic medications and Cardioprotective effect in cancer patients treated with cardiotoxic chemotherapeutics. A meta-analysis following PRISMA guidelines included observational studies comparing diabetic cancer patients treated with chemotherapy. Outcomes evaluated were heart failure (HF) incidence, HF exacerbation, atrial fibrillation (AF), hospitalization, and mortality. Data were independently extracted by five investigators from multiple databases up to January 20, 2025. Eight studies involving 27,015 patients were included. DM medication use may be associated with lower mortality (OR 0.50, p < 0.00001), HF incidence (OR 0.36, p = 0.007), HF exacerbation (OR 0.58, p < 0.0001), although heterogeneity was significant. Subgroup analysis revealed that SGLT-2 inhibitors may be associated with reduced mortality by 50%, HF incidence by 64%, and HF exacerbation by 49%. Hazard ratio analysis indicated SGLT-2 inhibitors use was associated with lower mortality risk in patients receiving cardiotoxic chemotherapy (HR 0.58, p = 0.001). Diabetic medications, particularly SGLT-2 inhibitors, may be associated with observational cardioprotective effect in cancer patients undergoing cardiotoxic chemotherapy. These findings highlight the need for further prospective trials to confirm subgroup benefits.