Dapagliflozin vs Empagliflozin Show Similar Clinical Outcomes in HF: JAMA
A cohort study in patients with heart failure (HF) found that dapagliflozin and empagliflozin provided comparable clinical outcomes. The authors note that further research and clinical trials are needed to confirm these results and guide treatment decisions. The study was published in JAMA Network Open by Seonghyeon Bu and colleagues.
Sodium-glucose cotransporter-2 inhibitors have emerged as foundational therapies across the spectrum of heart failure, irrespective of left ventricular ejection fraction. However, despite their widespread adoption, uncertainty has persisted regarding whether individual agents within the class differ in real-world effectiveness.
This was a retrospective cohort study shared by a clinical data warehouse, where integrative patient records were retrieved from the database of 8 medical centers affiliated with The Catholic University of Korea. Adult patients with diagnosed heart failure were screened between January 2021 and November 2023. Eligible patients received either dapagliflozin or empagliflozin and had a transthoracic echocardiography performed. Analyses of data were conducted between December 2023 and July 2025. In order to balance the two treatment groups, 1-to-1 propensity score matching was applied.
After matching, the final cohort consisted of 4,930 patients, with 2,465 patients in each treatment group. The mean (SD) age was 68.8 (13.4) years, and 2,944 patients (59.7%) were male. Median (IQR) follow-up time was 16.0 (8.0–27.0) months. Patients were divided based on left ventricular ejection fraction into three prespecified subgroups:
LVEF ≤40%: heart failure with reduced ejection fraction
LVEF 41%–49%: heart failure with mildly reduced ejection fraction
LVEF ≥ 50%: heart failure with preserved ejection fraction
The primary endpoint was a composite of cardiovascular death or hospitalization for heart failure. Secondary outcomes included cardiovascular death, hospitalization for heart failure, all-cause death, and overall cardiovascular hospitalization. Outcomes across cohorts were compared using adjusted hazard ratios derived from the matched cohort.
Key Findings
Primary Outcome:
The composite outcome occurred in 9.8% of patients receiving dapagliflozin (241 of 2,465) and 9.3% of patients receiving empagliflozin (229 of 2,465), with an AHR of 0.99 (95% CI, 0.83–1.19; P = 0.95).
LVEF ≤40% subgroup:
Events occurred in 14.9% (126 of 844) in the dapagliflozin group and 15.4% (132 of 855) in the empagliflozin group (AHR, 1.06; 95% CI, 0.83–1.35; P = 0.64).
LVEF 41%–49% subgroup:
Events occurred in 5.0% (17 of 343) vs 6.3% (22 of 350) (AHR, 1.28; 95% CI, 0.68–2.42; P = 0.45).
LVEF ≥50% subgroup:
Events occurred in 7.7% (98 of 1,278) vs 6.0% (75 of 1,260) (AHR, 0.80; 95% CI, 0.60–1.09; P = 0.32).
Interaction Test:
There was no significant between-group heterogeneity across LVEF strata (P for interaction = 0.32).
Secondary Outcomes:
No statistically significant differences were found between dapagliflozin and empagliflozin for cardiovascular death alone, heart failure hospitalization alone, all-cause mortality, or cardiovascular hospitalization.
In this large, multicenter cohort study, dapagliflozin and empagliflozin had similar rates of cardiovascular death and heart failure hospitalization across all heart failure phenotypes. These findings support the concept of therapeutic equivalence between the 2 SGLT2 inhibitors in heart failure care.
Reference:
Bu S, Jung M, Lee D, et al. Empagliflozin and Dapagliflozin Outcomes in Heart Failure. JAMA Netw Open. 2025;8(12):e2546865. doi:10.1001/jamanetworkopen.2025.46865
