Clinical Benefits of Sodium–Glucose Cotransporter 2 Inhibitors in Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure cases worldwide and is associated with substantial morbidity, recurrent hospitalizations, impaired quality of life, and high healthcare costs. Until recently, no pharmacological therapy had consistently demonstrated a prognostic benefit in this heterogeneous population. Sodium–glucose cotransporter 2 inhibitors (SGLT2i), initially developed for the treatment of type 2 diabetes mellitus, have emerged as a major therapeutic advance in heart failure across the entire spectrum of ejection fraction. Large randomized clinical trials have shown that SGLT2 inhibitors significantly reduce heart failure hospitalizations and improve health-related quality of life in patients with HFpEF, regardless of diabetic status. This review provides a comprehensive analysis of the clinical benefits of SGLT2 inhibitors in HFpEF, focusing on pathophysiological rationale, mechanisms of action, evidence from pivotal clinical trials, safety considerations, and current guideline recommendations.