Head-to-Head Comparison: Dapagliflozin vs Empagliflozin in CKD and Heart Failure
There is no evidence demonstrating superiority of either dapagliflozin or empagliflozin over the other in patients with CKD and heart failure—both SGLT2 inhibitors provide equivalent class effects with similar magnitude of benefit for renal and cardiovascular outcomes. 1
Evidence Supporting Equivalence
Renal Protection: Comparable Efficacy
Both agents demonstrate nearly identical renal benefits in their respective landmark trials:
Dapagliflozin (DAPA-CKD): Reduced the composite kidney outcome (≥50% sustained eGFR decline, ESKD, or renal death) by 44% (HR 0.56,95% CI 0.45-0.68) in patients with mean baseline eGFR 43.1 mL/min/1.73 m² and median UACR 949 mg/g 1
Empagliflozin (EMPA-KIDNEY): Reduced progression of kidney disease or cardiovascular death by 28% (HR 0.72,95% CI 0.64-0.82) in a broader population including patients with eGFR as low as 20 mL/min/1.73 m² 1
The slightly different hazard ratios reflect differences in trial design and patient populations rather than drug superiority—DAPA-CKD enrolled patients with more advanced albuminuria (UACR 200-5,000 mg/g), while EMPA-KIDNEY included patients with lower albuminuria thresholds (≥100 mg/g) 1
Cardiovascular Outcomes: Equivalent Benefits
Both agents provide similar cardiovascular protection:
Dapagliflozin: Reduced cardiovascular death or heart failure hospitalization by 29% (HR 0.71,95% CI 0.55-0.92) in CKD patients 1, 2
Empagliflozin: Reduced heart failure hospitalization by 35% in EMPA-REG OUTCOME and showed consistent benefits across the EMPEROR trials in patients with preserved and reduced ejection fraction 1
Both agents reduced all-cause mortality in their respective CKD trials, with dapagliflozin showing significant reduction (P < 0.004) 1, 2
Heart Failure Specific Data
In dedicated heart failure trials, both drugs demonstrate class-consistent effects:
DAPA-HF: Dapagliflozin reduced the primary outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85) in HFrEF patients, regardless of diabetes status 1
EMPEROR-Reduced and EMPEROR-Preserved: Empagliflozin showed similar magnitude benefits across the spectrum of ejection fractions, with consistent effects in patients with eGFR as low as 20 mL/min/1.73 m² 1, 3
Practical Clinical Algorithm
When choosing between dapagliflozin and empagliflozin:
Either agent is appropriate—select based on formulary availability, cost, and patient/provider familiarity 1
Dosing is identical for cardiovascular/renal protection: 10 mg once daily for both agents, regardless of eGFR level (as long as ≥20-25 mL/min/1.73 m²) 1, 4, 5
Both can be initiated at eGFR ≥20 mL/min/1.73 m² for cardiovascular and renal protection, though glycemic efficacy is lost below eGFR 45 mL/min/1.73 m² 1, 4, 5
Continue therapy even if eGFR declines below initiation threshold—both agents slow subsequent eGFR decline and maintain cardiovascular benefits 1, 5
Important Caveats
No Direct Comparison Trials Exist
All evidence comes from separate placebo-controlled trials with different inclusion criteria and endpoints—no head-to-head randomized controlled trial has compared dapagliflozin versus empagliflozin 1
The American Diabetes Association 2024 and 2025 guidelines treat both agents as interchangeable within the SGLT2 inhibitor class for CKD and heart failure indications 1
Shared Safety Profile
Both agents carry identical risks and require the same monitoring:
- Genital mycotic infections (approximately 6% vs 1% placebo) 4
- Euglycemic diabetic ketoacidosis risk—withhold during acute illness, surgery, or prolonged fasting 1, 4
- Transient eGFR dip of 3-5 mL/min/1.73 m² in first 4 weeks, which is reversible and does not indicate harm 4, 5
- Volume depletion risk, particularly in elderly patients or those on concurrent diuretics 4
Consistent Benefits Across Subgroups
Both dapagliflozin and empagliflozin demonstrate benefits: