Effects of SGLT2 inhibitors on cardiovascular, renal, and major safety outcomes in heart failure: A meta-analysis of randomized controlled trials

Aims: Sodium-glucose co-transporter 2 inhibitor (SGLT2i), initially introduced for the treatment of diabetes mellitus (DM), demonstrates cardiovascular and renal benefits in patients with heart failure (HF). We aimed to conduct a meta-analysis of its effects on cardiovascular, renal, and major safety outcomes in HF. Methods and results: PubMed, Embase, Cochrane Library, and Web of Science were searched using the terms of "SGLT2i and HF" or "SGLT2i *". Seven randomized, placebo-controlled trials comprising 14,113 HF patients (mean age, 66.0 years; female, 27.6%; DM, 58.9%) were included. SGLT2i treatment was associated with lower incidences (compared with placebo) of the composite outcomes of cardiovascular death or hospitalization for HF (HHF) (ratio risk [RR] 0.773; 95% confidence interval [CI], 0.719-0.831; p < 0.001; I-2 = 8.1%), cardiovascular death (RR 0.872; 95% CI, 0.788-0.964; p = 0.008; I-2 = 0.0%), HHF (RR 0.722; 95% CI, 0.657-0.793; p < 0.001; I2 = 15.4%) and serious decrease in renal function (RR 0.673; 95% CI, 0.549-0.825; p < 0.001; I-2 = 17.7%). SGLT2i treatment was associated with a lower incidence of serious adverse events (SAEs) (RR 0.867; 95% CI, 0.808-0.930; p < 0.001; I-2 = 60.1%), but a higher incidence of volume depletion (RR 1.177; 95% CI, 1.040-1.333; p = 0.010; I-2 = 0.0%). Analysis on patients without DM showed consistent results, except for cardiovascular death. Conclusion: SGLT2i treatment contributed to better cardiovascular and renal outcomes in patients with HF, regardless of the presence or absence of DM. SGLT2i also resulted in a lower incidence of SAEs, although a higher incidence of volume depletion was observed. (c) 2021 Elsevier B.V. All rights reserved.