Efficacy and Safety of SGLT2 Inhibitors in Non-Diabetic Patients with Heart Failure: A Systematic Review and Meta-Analysis

Abstract

Sodium-glucose cotransporter-2 inhibitors are an established therapy for heart failure, but a comprehensive synthesis of their efficacy in patients without diabetes across the full spectrum of left ventricular ejection fraction is needed. This systematic review and meta-analysis aimed to evaluate the effect of SGLT2 inhibitors in this specific population. A systematic search of major electronic databases was conducted to identify randomized controlled trials that enrolled adult patients with HF but without diabetes. The primary outcome was the composite of cardiovascular death or hospitalization for heart failure. The pooled analysis of four major RCTs demonstrated that SGLT2 inhibitors reduced the primary outcome ([HR] 0.78, 95% [CI] 0.72–0.86) with no statistical heterogeneity (I²=0.0%). This therapeutic benefit was consistent across patients with both reduced and preserved LVEF (P = 0.47). These findings support using SGLT2 inhibitors as a foundational therapy for patients with HF, irrespective of LVEF phenotype, in the non-diabetic population.