SGLT2 Inhibitors in Cardio-Oncology

Background: According to available evidence, sodium-glucose cotransporter-2 inhibitors (SGLT2i) may confer cardioprotection in patients with cancer undergoing chemotherapy. Objectives: The objective of the study was to evaluate the impact of SGLT2i on all-cause mortality and heart failure (HF) outcomes in this population. Methods: We searched PubMed, Cochrane CENTRAL, and Embase through August 2025 for studies of SGLT2i in adult patients with cancer. Random-effects models were used to pool effects for all-cause mortality and an HF composite (new-onset HF and/or HF hospitalization) in cancer patients >18 years. Meta-regression tested effect modification by beta-blockers, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, age, and sex. Results: Thirteen observational studies were included, for a total of 107,126 patients. The median age was 67.6 years (IQR: 62.5-71.0); median follow-up was 24 months (IQR: 19.2-29.0), nearly all patients had diabetes mellitus. SGLT2i were associated with lower all-cause mortality (risk ratio [RR]: 0.47; 95% CI: 0.38-0.58; I2 = 96.30%; P < 0.001), with no effect modification by background therapies, age, or sex (all P > 0.05). The HF composite was also significantly reduced (RR: 0.48; 95% CI: 0.29-0.78; I2 = 87.01%), again with no evidence that background therapies modified the effect (all P > 0.05). Risk of atrial fibrillation/atrial flutter was lower with SGLT2i (RR: 0.57; 95% CI: 0.42-0.76; I2 = 66.4%; P < 0.001). Safety outcomes were not increased in the SGLT2i arm. Conclusions: In patients with cancer, SGLT2i appear safe and are associated with fewer deaths and HF events, although substantial heterogeneity was observed across studies. Randomized controlled trials are warranted to confirm these hypothesis-generating findings.