Real-World Analysis Links Empagliflozin to Lower Cardiorenal Event Risk Versus Dapagliflozin in T2D

As SGLT2 inhibitors continue to redefine the standard of care in type 2 diabetes, questions are shifting from whether to use them to which agent to choose for individual patients.

Both dapagliflozin and empagliflozin have established themselves as foundational therapies, supported by robust clinical trial evidence from landmark cardiovascular outcomes trials like EMPA-REG OUTCOME and DECLARE-TIMI 58 to later heart failure trials such as DAPA-HF and EMPEROR-Reduced, along with chronic kidney disease-focused studies like DAPA-CKD and EMPA-KIDNEY, further reinforcing consistent cardiorenal benefits that extend beyond glycemic control and beyond diabetes itself.

Despite this robust and largely concordant body of randomized trial evidence, direct comparisons between individual SGLT2 inhibitors remain limited. Cross-trial differences in baseline cardiovascular risk, renal function, and inclusion criteria complicate efforts to draw definitive conclusions about relative efficacy, leaving clinicians to extrapolate across differing datasets. As these agents are increasingly initiated earlier in the disease course and in patients without established atherosclerotic cardiovascular disease, the absence of head-to-head data becomes more clinically relevant.

Understanding whether meaningful differences exist between agents could have important implications for tailoring therapy, optimizing outcomes, and aligning treatment decisions with individual patient risk profiles.

New data presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 by Lana Tannous, MD, New York Medical College and Landmark Medical Center, seek to address this gap through a retrospective cohort study using data from the TriNetX network.

She and colleagues conducted propensity score matching on demographics, cardiovascular and renal comorbidities, concomitant medications, and laboratory values in order to yield 2 well-balanced cohorts, with 307,562 patients in each group.

Upon analysis, empagliflozin was associated with a reduced risk of major adverse cardiovascular events (3.9% vs 4.1%; hazard ratio [HR], 1.10; 95% CI, 1.07-1.12; P <.001), heart failure exacerbation (19.2% vs 20.5%; HR, 1.11; 95% CI, 1.09-1.13; P <.001), and death (3.0% vs 3.3%; HR, 1.12; 95% CI, 1.09-1.15; P <.001). Investigators additionally highlighted reduced risks of acute kidney injury (7.8% vs 8.6%; HR, 1.12; 95% CI, 1.10-1.14; P <.001), dialysis (0.3% vs 0.5%; HR, 1.46; 95% CI, 1.35-1.58; P < .001), and all-cause hospitalization/ER visits (27.9% vs 29.9%; HR, 1.12; 95% CI, 1.11-1.13; P <.001) with empagliflozin compared to dapagliflozin.

Of note, there was no significant difference in stroke risk between the empagliflozin and dapagliflozin groups (1.3% vs 1.3%; HR, 1.01; 95% CI, 0.97-1.06; P >.05).

“Results showed empagliflozin was associated with modestly lower risks of cardiovascular events, heart failure exacerbations, death, acute kidney injury, dialysis, and all-cause hospitalization/ER visits compared with dapagliflozin, despite only a small difference in glycemic control,” Tannous and colleagues wrote. “These findings suggest potential cardiorenal safety and effectiveness advantages of empagliflozin that warrant prospective confirmation.”

References

1. Tannous L, Agrawal S, Assis PR, et al. Real-World Comparative Effectiveness of Dapagliflozin and Empagliflozin on Cardiovascular, Renal, and Metabolic Outcomes. Poster presented at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2026 in Las Vegas, Nevada, April 22-24, 2026.

2. Campbell P. Dapagliflozin Safe and Effective in Stage 4 Chronic Kidney Disease, DAPA-CKD Analysis Finds. HCPLive. July 20, 2021. Accessed April 22, 2026. https://www.hcplive.com/view/dapagliflozin-safe-and-effective-in-stage-4-chronic-kidney-disease-dapa-ckd-analysis-finds

3. Iapoce C. EMPA-KIDNEY Stopped Early Due to Clear Positive Efficacy with Empagliflozin. HCPLive. March 16, 2022. Accessed April 22, 2026. https://www.hcplive.com/view/empa-kidney-stopped-early-clear-positive-efficacy-empagliflozin