Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Heart Failure With Preserved Ejection Fraction: A Systematic Review.

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by impaired ventricular filling and increased heart failure hospitalizations. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardiovascular and renal benefits in various heart failure populations, but their effects on HFpEF remain an area of growing interest. This study aims to evaluate the impact of SGLT2 inhibitors on key clinical outcomes in patients with HFpEF, including cardiovascular death, hospitalization for heart failure, exercise capacity, symptoms (as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ)), kidney disease progression, and other renal outcomes. A systematic review of randomized controlled trials (RCTs) assessing the effects of SGLT2 inhibitors (empagliflozin, dapagliflozin, sotagliflozin, canagliflozin, and ertugliflozin) in HFpEF patients was conducted. This systematic review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) principles. The literature was searched using open-access, full-text English papers from January 2015 to April 2025 across PubMed, Embase, and the Cochrane Library. A total of 108 articles were retrieved through the initial search. After screening and checking for eligibility according to the pre-specified inclusion criteria, the methodological quality was assessed in 17 included studies using the Mixed Methods Appraisal Tool (MMAT) score. The MMAT Score 4 indicates a medium risk of bias (ROB), and the MMAT Score 5 indicates a low ROB. Ten studies had low ROB and were classified as "high quality." Seven had uncertain ROB, lowering the evidence by one point to "moderate quality," while one study had a high ROB. SGLT2 inhibitors were associated with significant reductions in cardiovascular death and heart failure-related hospitalizations. Improvements in KCCQ total symptom scores were observed, indicating enhanced patient-reported outcomes. The renal benefits of SGLT2 inhibitors were evident, with a reduction in kidney disease progression and a marked decrease in cardiovascular-related renal outcomes.