Which SGLT2 (sodium-glucose cotransporter 2) inhibitor, dapagliflozin (Forxiga) or empagliflozin (Jardiance), has better cardiovascular outcomes in patients with type 2 diabetes and established cardiovascular disease?

Cardiovascular Outcomes: Empagliflozin vs Dapagliflozin

Empagliflozin demonstrates superior cardiovascular mortality reduction compared to dapagliflozin, with a 38% reduction in cardiovascular death versus no significant effect with dapagliflozin in the overall population, making empagliflozin the preferred choice for patients with type 2 diabetes and established atherosclerotic cardiovascular disease when cardiovascular mortality is the primary concern. 1, 2

Key Cardiovascular Outcome Differences

Cardiovascular Mortality

• Empagliflozin reduced cardiovascular death by 38% (HR 0.62; 95% CI 0.49-0.77) in the EMPA-REG OUTCOME trial, which enrolled 7,020 patients with type 2 diabetes and established ASCVD followed for a median of 3.1 years 1, 3
• Dapagliflozin showed no significant effect on cardiovascular death in the overall DECLARE-TIMI 58 population 2
• This represents the most clinically meaningful difference between the two agents when prioritizing mortality outcomes 2

All-Cause Mortality

• Empagliflozin reduced all-cause mortality by 32% (HR 0.68; 95% CI 0.57-0.82) 1
• Dapagliflozin did not demonstrate a statistically significant reduction in all-cause mortality in DECLARE-TIMI 58 (HR 0.93; 95% CI 0.82-1.04) 4

Major Adverse Cardiovascular Events (MACE)

• Both agents showed similar modest reductions in the 3-point MACE composite (cardiovascular death, non-fatal MI, non-fatal stroke) 1, 2
• Empagliflozin reduced MACE by 14% (HR 0.86; 95% CI 0.74-0.99) 1, 3
• Dapagliflozin demonstrated cardiovascular safety but not superiority for MACE (HR 0.93; 95% CI 0.84-1.03) 4
• Meta-analyses confirm no significant difference between the two agents for MACE, MI, or stroke 5, 6

Heart Failure Hospitalization

• Both agents provide robust and comparable reductions in heart failure hospitalization 2
• Empagliflozin reduced hospitalization for heart failure by 35% (HR 0.65; 95% CI 0.50-0.85) 1, 2
• Dapagliflozin reduced hospitalization for heart failure by 27% (HR 0.73; 95% CI 0.61-0.88) 2, 4
• The difference in heart failure outcomes between the two agents is not statistically significant 5, 6

Clinical Decision Algorithm

For patients with type 2 diabetes and established ASCVD:

1. Primary concern is cardiovascular mortality or all-cause mortality → Choose empagliflozin 10-25 mg daily based on its proven 38% reduction in cardiovascular death 1, 3

2. Primary concern is heart failure hospitalization → Either agent is appropriate, as both provide substantial and comparable reductions (empagliflozin 35%, dapagliflozin 27%) 1, 2, 4

3. History of or high risk for atrial fibrillation → Consider dapagliflozin, which demonstrated superior efficacy in preventing atrial fibrillation compared to empagliflozin in meta-analysis 5

4. Chronic kidney disease with albuminuria → Both agents provide renal protection; empagliflozin reduced incident or worsening nephropathy by 39% 1, while dapagliflozin reduced composite renal outcomes by 44-47% 4

Important Clinical Context

Trial Population Differences

• EMPA-REG OUTCOME enrolled patients with 99% having established ASCVD at baseline, representing a very high-risk population 1
• DECLARE-TIMI 58 enrolled a broader population with only approximately 40% having established ASCVD, which may explain the differential mortality benefits 7, 4
• The mortality benefit of empagliflozin was demonstrated specifically in patients with established cardiovascular disease, which aligns with the question's target population 1, 3

Guideline Recommendations

• The American College of Cardiology recommends empagliflozin for patients with type 2 diabetes and established ASCVD to reduce cardiovascular mortality and heart failure hospitalization 1
• The American Diabetes Association recommends SGLT2 inhibitors with demonstrated cardiovascular benefit for patients with type 2 diabetes and established ASCVD 2
• Both agents have proven cardiovascular benefits and are appropriate choices, but empagliflozin has the unique distinction of proven cardiovascular mortality reduction 1, 2

Common Pitfalls to Avoid

• Do not assume all SGLT2 inhibitors have identical cardiovascular effects—the mortality benefit is specific to empagliflozin in the established ASCVD population 1, 2
• Do not withhold these agents in patients with moderate renal impairment (eGFR 30-60 mL/min/1.73 m²), as cardiovascular and renal benefits are preserved and potentially enhanced in this population 3, 8
• Do not prescribe based solely on glucose-lowering efficacy, as the cardiovascular benefits are independent of glycemic control 1, 4