The Role of SGLT2 Inhibitors on Heart Failure Outcomes in Nondiabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with heart failure (HF). However, studies examining their benefits exclusively in nondiabetic patients on various HF outcomes are limited. By conducting a MEDLINE and ClinicalTrials.gov search for randomized controlled trials, we identified 4 studies on SGLT2i with data on HF outcomes in nondiabetic patients and performed a meta-analysis. There were 10,638 nondiabetic patients, with 5316 patients in the SGLT2i group and 5322 in the placebo group included in this meta-analysis. The composite of worsening HF (hospitalization for HF or urgent visit for HF) or cardiovascular death had 726 events (13.66%) in the SGLT2i group and 907 (17.04%) in the placebo group, with a hazard ratio (HR) of 0.78 and 95% confidence interval (CI) of 0.71-0.86 ( P < 0.0001). There were 551 events (10.36%) of hospitalization for HF in the SGLT2i group, compared with 751 (14.11%) in the placebo group with an HR of 0.71 (95% CI, 0.62-0.81; P < 0.0001). Cardiovascular death occurred in 396 patients (7.45%) in the SGLT2i group and 452 (8.49%) in the placebo group, with an HR of 0.88 (95% CI, 0.77-1.00; P = 0.059). All-cause mortality occurred in 552 patients (10.38%) in the SGLT2i group and 586 (11.01%) in the placebo group, with an HR of 0.95 (95% CI, 0.84-1.07; P = 0.37). This study showed that in patients with HF without diabetes mellitus, SGLT2i improve HF outcomes, including a significant decrease in hospitalizations for HF and a favorable response for the outcome of cardiovascular death.