SGLT-2 Inhibitors in Prevention of Chemotherapy-Induced Cardiotoxicity: Systematic Review and Meta-analysis

Abstract Background Chemotherapy is associated with significant cardiotoxicity. Although other guideline directed medications for heart failure are effective in managing or preventing these cardiotoxic effects, the potential role of sodium-glucose cotransporter-2 (SGLT2) inhibitors remain incompletely understood. Objectives This study aims to systematically review high-quality studies to evaluate the cardiovascular outcomes associated with SGLT2 inhibitor use in cancer patients undergoing chemotherapy. Methods We conducted a meta-analysis of cohort studies comparing cardiovascular outcomes between cancer patients receiving SGLT2 inhibitors and those not receiving SGLT2 inhibitors. Cochrane Central Register, clinicaltrials.gov, PubMed, Embase, and Google Scholar were searched from inception to May 2025. Primary outcome was all-cause mortality. Secondary outcomes included cardiac events, and cardiac dysfunction. We used fixed and random effect binomial meta-analysis fit using the Mantel-Haenszel method for each outcome of interest. All analyses were conducted using the ‘meta’ package in R Statistical Software. Results Eleven cohort studies comprising 2,689,260 patients were included, of whom 29,958 received SGLT2 inhibitors. SGLT2 inhibitor use was significantly associated with reduced all-cause mortality (OR 0.27, 95% CI 0.25–0.28), cardiac events (OR 0.49, 95% CI 0.49–0.53), cardiac dysfunction (OR 0.62, 95% CI 0.56–0.69), and heart failure hospitalizations (OR 0.67, 95% CI 0.61–0.75) compared to non-use. Conclusions SGLT2 inhibitors demonstrate robust cardioprotective effects in cancer patients receiving chemotherapy, significantly reducing mortality, heart failure hospitalizations, and major cardiac events. These findings support the integration of SGLT2 inhibitors into cardio-oncology strategies, particularly for patients at high risk of chemotherapy-induced cardiotoxicity.