Effect of SGLT2 inhibitors on heart failure outcomes in patients with and without diabetes: A systematic review and meta‑analysis of randomized controlled trials

Heart failure (HF) is a debilitating condition with high morbidity and mortality rates worldwide.Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exhibit cardiovascular (CV) and renal protective effects beyond glucose lowering, and may serve a role in managing HF across numerous patient populations, including non-diabetics.Therefore, the present systematic review and meta-analysis aimed to evaluate the efficacy of SGLT2i in reducing HF hospitalizations, CV mortality and adverse events in patients with and without type 2 diabetes mellitus.Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, comprehensive literature searches were conducted across PubMed, Scopus, Web of Science and Cochrane Central databases up to May 2025.Randomized controlled trials (RCTs; phases II-IV) enrolling adults with HF, irrespective of ejection fraction or diabetes status, comparing SGLT2i with placebo or standard-of-care were included in the present study.Outcomes analyzed encompassed HF hospitalizations, CV and all-cause mortality, adverse events and patient-reported quality of life measures.Meta-analysis was performed with RevMan 5.4 using a random-effects model.Data from 28 RCTs, including numerous high-quality trials, consistently demonstrated that SGLT2i significantly reduced the risk of first and total hospitalization for HF by 24% [odds ratio (OR)=0.76;95% CI: 0.64-0.91;P=0.002; I²=0%] and 33% (OR=0.67;95% CI: 0.63-0.72;P