Association between sodium-glucose co-transporter-2 inhibitors and cardiac outcomes in cancer patients: a systematic review and meta-analysis

BACKGROUND The beneficial effects of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on adverse cardiac outcomes in diabetic patients are well-established. However, the effects of SGLT2i against cancer therapy-related cardiotoxicity remain understudied. We investigated the association between SGLT2i and cardiac outcomes in cancer patients. METHODS PubMed, Embase, and the Cochrane Library were searched from their inception until September 30, 2024 for studies evaluating the effects of SGLT2i in patients with cancer. The primary outcomes included incident heart failure (HF), HF exacerbation, HF hospitalization, atrial fibrillation/atrial flutter (AF/AFL), myocardial infarction, and all-cause mortality. The secondary outcomes included acute kidney injury and sepsis. Odds ratio (OR) with 95% CI was pooled. RESULTS Thirteen studies with 85,596 patients were included. Compared to non-SGLT2i use, SGLT2i treatment was associated with lower risks of incident HF (OR = 0.51, 95% CI: 0.32–0.79, P = 0.003), HF exacerbation (OR = 0.74, 95% CI: 0.63–0.87, P < 0.001), AF/ AFL (OR = 0.67, 95% CI: 0.55–0.82, P < 0.001), myocardial infarction (OR = 0.61, 95% CI: 0.41–0.90, P = 0.01), and all-cause mortality (OR = 0.44, 95% CI: 0.28–0.69, P < 0.001), but not for HF hospitalization (OR = 0.58, 95% CI: 0.22–1.55, P = 0.28). As for safety outcomes, SGLT2i use was associated with lower risks of acute kidney injury (OR = 0.68, 95% CI: 0.57–0.81, P < 0.001) and sepsis (OR = 0.32, 95% CI: 0.23–0.44, P < 0.001). CONCLUSIONS SGLT2i were associated with lower risks of incident HF, HF exacerbation, AF/AFL, myocardial infarction, all-cause mortality, acute kidney injury, and sepsis in cancer patients.