What is the preferred SGLT2 (sodium-glucose cotransporter 2) inhibitor, dapagliflozin or empagliflozin, for patients with type 2 diabetes and cardiovascular disease from a cardiac perspective?

Dapagliflozin vs. Empagliflozin for Cardiac Outcomes in Type 2 Diabetes

Both dapagliflozin and empagliflozin demonstrate significant cardiovascular benefits in patients with type 2 diabetes and cardiovascular disease, with dapagliflozin showing slightly stronger evidence for heart failure with preserved ejection fraction (HFpEF), while empagliflozin has more robust data for established cardiovascular disease reduction.

Cardiovascular Outcomes Comparison

• Both SGLT2 inhibitors significantly reduce hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease, with empagliflozin showing a 35% reduction and dapagliflozin showing a 27% reduction in respective trials 1
• Empagliflozin demonstrated a 38% reduction in cardiovascular death in the EMPA-REG OUTCOME trial in patients with established cardiovascular disease 1
• Dapagliflozin reduced the risk of cardiovascular death by 18% in the DELIVER trial for patients with heart failure and preserved ejection fraction (>40%) 1
• Both medications show consistent benefits regardless of baseline heart failure status 1

Heart Failure Benefits

• Dapagliflozin has strong evidence from the DAPA-HF trial showing a 26% reduction in the composite outcome of worsening heart failure or cardiovascular death (HR 0.74) in patients with reduced ejection fraction (≤40%) 1
• Empagliflozin demonstrated a 21% reduction in the composite of cardiovascular death or hospitalization for heart failure in the EMPEROR-Reduced trial 1
• Dapagliflozin has additional evidence from the DELIVER trial showing an 18% reduction in heart failure outcomes in patients with preserved ejection fraction (>40%), making it particularly valuable for this common form of heart failure 1
• The benefits of both medications on heart failure outcomes appear to be a class effect and are consistent regardless of the presence or absence of type 2 diabetes 1

Clinical Decision Algorithm

For patients with type 2 diabetes and cardiovascular disease:

1. If patient has heart failure with preserved ejection fraction (HFpEF):

   • Prefer dapagliflozin based on the DELIVER trial evidence 1

2. If patient has heart failure with reduced ejection fraction (HFrEF):

   • Either medication is appropriate, with dapagliflozin showing a 26% reduction and empagliflozin showing a 21% reduction in heart failure outcomes 1

3. If patient has established atherosclerotic cardiovascular disease without heart failure:

   • Consider empagliflozin based on the robust 38% reduction in cardiovascular death in EMPA-REG OUTCOME 1

4. If patient has chronic kidney disease with cardiovascular risk:

   • Both medications show benefits, but empagliflozin has demonstrated consistent effects across categories of eGFR and urine albumin-creatinine ratio 2

Cost Considerations

• According to 2021 pricing data, the median monthly cost (AWP) for maximum approved daily doses was similar:
  • Dapagliflozin 10mg: $621
  • Empagliflozin 25mg: $627 1

Important Caveats

• The cardiovascular benefits of both medications appear to be independent of their glucose-lowering effects 1
• Benefits are seen regardless of baseline heart failure status, suggesting preventive effects 1
• A recent network meta-analysis suggested that canagliflozin may have the highest probability of reducing heart failure hospitalization (95.5%), followed by sotagliflozin (66.0%) and empagliflozin (57.2%) among all SGLT2 inhibitors 3
• When focusing specifically on heart failure trials, sotagliflozin ranked highest for reducing the composite of cardiovascular death/heart failure hospitalization (97.6%), followed by empagliflozin (58.4%) and dapagliflozin (44.0%) 3