What is the difference between empagliflozin (Empagliflozin) and dapagliflozin (Dapagliflozin) in terms of treatment for patients with established cardiovascular disease or at high risk of cardiovascular events?

Empagliflozin vs Dapagliflozin: Comparative Effectiveness

Both empagliflozin and dapagliflozin demonstrate equivalent cardiovascular effectiveness in patients with type 2 diabetes, with no clinically meaningful differences in major adverse cardiovascular events, heart failure outcomes, or mortality. 1

Key Evidence from Direct Comparison

The most recent and highest quality evidence comes from a 2024 Danish nationwide target trial emulation directly comparing these agents:

• No difference in 6-year cardiovascular outcomes between empagliflozin and dapagliflozin initiators (10.0% vs 10.0%; risk difference 0.0%, 95% CI -0.9% to 1.0%) 1
• This equivalence held across all subgroups including patients with established atherosclerotic cardiovascular disease and those with heart failure 1
• The study included 36,670 empagliflozin and 20,606 dapagliflozin initiators, controlling for 57 potential confounders 1

Individual Trial Performance

Empagliflozin (EMPA-REG OUTCOME)

• 14% reduction in major adverse cardiovascular events (HR 0.86,95% CI 0.74-0.99) in patients with established cardiovascular disease 2, 3
• 38% reduction in cardiovascular mortality (3.7% vs 5.9%) - the most robust mortality benefit among SGLT2 inhibitors 2
• 35% reduction in heart failure hospitalization (2.7% vs 4.1%) 2
• 32% reduction in all-cause mortality (5.7% vs 8.3%) 3
• 100% of enrolled patients had established cardiovascular disease 2

Dapagliflozin (DECLARE-TIMI 58)

• Did not significantly reduce major adverse cardiovascular events as a standalone outcome 2
• 17% reduction in cardiovascular death or heart failure hospitalization (4.9% vs 5.8%) 2
• 27% reduction in heart failure hospitalization 2
• Only 41% had established cardiovascular disease at baseline (59% were primary prevention) 2

Heart Failure Specific Evidence

Both agents demonstrate robust benefits across the ejection fraction spectrum:

• DAPA-HF: Dapagliflozin reduced worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85) in HFrEF patients 2, 4
• EMPEROR-Reduced: Empagliflozin reduced cardiovascular death or heart failure hospitalization by 21% (HR 0.79,95% CI 0.69-0.90) in HFrEF patients 4
• DELIVER and EMPEROR-Preserved: Both agents effective in heart failure with preserved ejection fraction 2, 4

Renal Protection

• Dapagliflozin demonstrated 44% reduction in composite renal outcomes (HR 0.56,95% CI 0.45-0.68) in the DAPA-CKD trial 2, 4
• Empagliflozin showed 39% reduction in chronic kidney disease progression (12.7% vs 18.8%) 2
• Both agents provide renoprotective effects independent of diabetes status 4

Clinical Decision Algorithm

For patients with established cardiovascular disease:

• Either agent is appropriate based on equivalent real-world effectiveness 1
• Empagliflozin has stronger evidence for cardiovascular mortality reduction in the trial setting 2, 3

For patients with heart failure (any ejection fraction):

• Both agents equally recommended regardless of diabetes status 2, 4
• Choose based on formulary, cost, and patient preference 1

For patients with chronic kidney disease:

• Dapagliflozin has specific trial evidence in CKD populations with UACR 200-5,000 mg/g 2, 4

For primary prevention (no established CVD):

• Both agents appropriate, though dapagliflozin has more trial data in this population 2

Safety Considerations

• Both agents carry similar risks: genital infections, urinary tract infections, volume depletion, and euglycemic ketoacidosis 4, 3
• Monitor for volume depletion when combining with diuretics 4
• No significant differences in adverse event profiles between the two agents 1

Cost-Effectiveness

• Empagliflozin demonstrated cost-effectiveness versus dapagliflozin in some analyses (ICER €965 per QALY in Greece, $3,054 per QALY in US models) 5, 6
• However, real-world outcomes show no clinical difference, making formulary status and patient cost the primary economic considerations 1