When to choose empagliflozin (Empagliflozin) over dapagliflozin (Dapagliflozin) and is their use recommended in patients with severe impaired renal function (eGFR below 15)?

Empagliflozin vs Dapagliflozin: Selection Criteria and Use in Severe Renal Impairment

Both empagliflozin and dapagliflozin can be initiated at eGFR ≥20 mL/min/1.73m², but neither should be started in patients with eGFR <15 mL/min/1.73m² or in those on dialysis. 1, 2

Choosing Between Empagliflozin and Dapagliflozin

Cardiovascular Considerations

• Heart Failure: Both medications show significant benefits in reducing heart failure hospitalizations (empagliflozin: HR 0.65 [95% CI 0.50-0.85]; dapagliflozin: HR 0.73 [95% CI 0.61-0.88]) 1
• Cardiovascular Death: Empagliflozin shows a stronger reduction in cardiovascular death (HR 0.62 [95% CI 0.49-0.77]) compared to dapagliflozin (HR 0.98 [95% CI 0.82-1.17]) 1
• Prefer empagliflozin in patients with established cardiovascular disease who need reduction in cardiovascular mortality 1

Renal Considerations

• Chronic Kidney Disease: Dapagliflozin demonstrated significant benefits in the DAPA-CKD trial with a 39% reduction in the primary composite outcome (HR 0.61 [95% CI 0.51-0.72]) 1, 2
• Empagliflozin showed similar benefits in the EMPA-KIDNEY trial with a 28% reduction in kidney disease progression (HR 0.72 [95% CI 0.64-0.82]) 1
• Prefer dapagliflozin in patients with CKD without established cardiovascular disease based on more robust renal outcome data 2, 3

eGFR Considerations

• Both medications can be initiated at eGFR ≥20 mL/min/1.73m² 1, 2
• Both should be continued even if eGFR falls below 20 mL/min/1.73m² (but above 15) after initiation 2
• Neither should be initiated in patients with eGFR <15 mL/min/1.73m² or in those on dialysis 2, 4, 5

Algorithm for Selection

1. For patients with established cardiovascular disease and need for CV mortality reduction:

   • Choose empagliflozin 10-25mg daily 1

2. For patients with chronic kidney disease without established CVD:

   • Choose dapagliflozin 10mg daily 2, 3

3. For patients with heart failure (with reduced or preserved ejection fraction):

   • Either medication is appropriate (class effect) 1, 6

4. For patients with eGFR between 20-45 mL/min/1.73m²:

   • Either medication can be used; both have demonstrated benefits in this range 1, 2

Important Considerations for eGFR <15 mL/min/1.73m²

• Do not initiate either medication when eGFR <15 mL/min/1.73m² 2
• The glucose-lowering effect of both medications is minimal at eGFR <45 mL/min/1.73m², but cardiovascular and renal benefits persist 2
• If a patient's eGFR drops below 15 mL/min/1.73m² while on treatment:
  • Consider continuing therapy until dialysis initiation if the patient is tolerating the medication well 2
  • Monitor for volume depletion and hypotension 2
  • Discontinue when dialysis is initiated 2

Safety Considerations

• Volume depletion: Monitor volume status and blood pressure in all patients, particularly those with eGFR <30 mL/min/1.73m² 2
• Diabetic ketoacidosis: Rare but serious risk, especially in insulin-deficient patients 2
• Genital mycotic infections: Most common adverse effect, particularly in women 2
• Acute kidney injury: Initial eGFR decline of 2-4 mL/min/1.73m² is expected and not a reason to discontinue therapy 3

Switching Between Medications

When switching from dapagliflozin to empagliflozin (or vice versa), no significant differences in glycemic control or renal function have been observed 7. Both medications demonstrate similar clinical outcomes in patients without established cardiovascular disease, chronic kidney disease, or heart failure, supporting a class effect 8.