Efficacy of Empagliflozin versus Dapagliflozin in Heart Failure with Preserved Ejection Fraction: A Randomized Controlled Trial

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases and remains a therapeutic challenge. Sodium-glucose cotransporter2 (SGLT2) inhibitors have emerged as the first pharmacologic class to demonstrate consistent benefit in this population. However, head-to-head comparative data between empagliflozin and dapagliflozin in HFpEF remain scarce, particularly in South Asian cohorts. The present trial was undertaken to compare the efficacy and tolerability of these two agents in symptomatic HFpEF patients over a one-year follow-up. Methods: A prospective, randomized, open-label, parallel-group trial was conducted at a tertiary care centre in Pakistan over twelve months. Sixty patients aged 40–75 years with left ventricular ejection fraction ≥50%, NYHA class II–III symptoms, and elevated NT-proBNP were enrolled and randomized 1:1 to empagliflozin 10 mg once daily (n=30) or dapagliflozin 10 mg once daily (n=30) on top of guideline-directed therapy. Co-primary outcomes were change in Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score (KCCQ-CS) and 6-minute walk distance (6MWD) at 12 months. Secondary outcomes included NTproBNP reduction, NYHA class improvement, heart failure hospitalization, and adverse events. Intention-to-treat analysis was performed using SPSS v26; p<0.05 was considered significant. Results: Mean age was 62.4±8.1 years; 56.7% were female. KCCQ-CS improved by 14.8±5.6 points with empagliflozin and 13.9±5.9 points with dapagliflozin (p=0.547). The 6MWD increased by 48.7±18.2 m and 45.3±19.6 m, respectively (p=0.491). NT-proBNP fell by 31.2% versus 28.7% (p=0.612). Heart failure hospitalization occurred in 3 (10.0%) and 4 (13.3%) patients (p=0.687). Genitourinary infections were the most frequent adverse event (10.0% vs 13.3%; p=0.687). No deaths occurred. Conclusion: Empagliflozin and dapagliflozin produced comparable and clinically meaningful improvements in symptoms, functional capacity, and natriuretic peptide levels in HFpEF, with similar safety profiles, supporting interchangeability within the SGLT2 inhibitor class.