Efficacy and safety of sodium-glucose co-transporter 2 inhibitors in heart failure patients: A systematic review and meta-analysis of randomized controlled trials

Background and Objectives: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) significantly reduce the risk of cardiovascular events in patients with type 2 diabetes mellitus (T2DM). However, the effectiveness of SGLT2is in heart failure (HF) treatment has not yet been established. The aim of this meta-analysis was to assess the efficacy and safety of SGLT2is in HF treatment by focusing on cardiovascular death (CVD), hospitalization for HF (HHF), and a composite of CVD and HHF. Methods: We searched literature sources in PubMed, EMBASE, and Cochrane Library up until December 20, 2020. Only randomized controlled trials were included in this meta-analysis. We compared the treatment and placebo groups in terms of their associated risks of CVD and HHF and their safety endpoints. The Cochrane tool for assessing risk of bias in randomized trials was applied. Results: The 10 selected studies included 17,043 HF patients and dapagliflozin, empagliflozin, canagliflozin, ertugliflozin, and sotagliflozin as experimental arms. At least 4 included studies were with high quality. For CVD, HHF, and their composite, the pooled risk ratio estimates were 0.87 (95% confidence interval [CI], 0.78–0.96; P = 0.004), 0.70 (95% CI, 0.65–0.76; P