Effects of SGLT2 Inhibitors in Patients with Cancer and Diabetes Mellitus: A Systematic Review and Meta-analysis

Abstract Aims Cardiovascular disease (CVD) and cancer represent significant global health challenges. An overlap between oncology and cardiology is compounded by cancer therapies, which are known to have cardiotoxic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed for treating diabetes, have shown promising cardiovascular benefits in non-cancer populations, particularly in preventing heart failure (HF) and reducing HF-related hospitalization and mortality in large randomized controlled trials (RCTs) across the spectrum of left ventricular ejection fraction (LVEF). However, their potential cardioprotective role in cancer patients remains unclear. This systematic review and meta-analysis evaluated cardiovascular outcomes in cancer patients with type 2 diabetes undergoing chemotherapy with concomitant use of SGLT2i compared to those not using SGLT2i. Subgroup analyses were performed to explore patients without baseline HF and patients treated exclusively with anthracyclines. Methods and Results A systematic review identified eleven observational retrospective studies (n=104,327 patients). Based on the National Institutes of Health Quality Assessment Tool (NIH-QAT) checklist, 2 studies were at moderate risk of bias, while all other included studies had a low risk of bias. Meta-analysis indicated that the use of SGLT2i was associated with a significant reduction in all-cause mortality (0.47, 95% CI 0.33-0.67, P<0.0001) and risk of HF hospitalization (0.44, 95% CI 0.27-0.72, P=0.001). Conclusion SGLT2i use may be associated with a significant reduction in all-cause mortality and risk of HF hospitalization in actively treated cancer patients with type 2 diabetes. Our study highlights the need for further investigation through prospective RCTs to confirm the efficacy and safety of SGLT2i in attenuating cardiotoxicity and supporting cardiovascular health in oncology settings.