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 < 0.001), and 0.76 (95% CI, 0.71–0.81; P < 0.001), respectively. The incidence of volume depletion, hypoglycemia events, fractures, acute renal injury, and urogenital tract infection was not significantly higher in the SGLT2i group than in the placebo group. Stratified analyses showed similar efficacy and safety results for HF patients with T2DM, those without T2DM, and those being treated with different types of SGLT2is. Conclusions: This meta-analysis demonstrated that various SGLT2is significantly decreased the risks of CVD and HHF in HF patients with and without T2DM. It also showed that clinical administration of SGLT2is was relatively safe in terms of the aforementioned risk factors. SGLT2is might embrace broader clinical application in future HF treatment