What is the estimated glomerular filtration rate (eGFR) cut off for initiating Dapagliflozin (Forxiga) in patients with impaired renal function?

Dapagliflozin eGFR Cut-Off for Initiation in Patients with Impaired Renal Function

Dapagliflozin should not be initiated for glycemic control when eGFR is <45 mL/min/1.73 m², but can be initiated for cardiovascular and renal benefits in patients with eGFR as low as 25 mL/min/1.73 m². 1, 2

eGFR Thresholds for Dapagliflozin Initiation

For Glycemic Control

• Dapagliflozin can be initiated at 10 mg daily in patients with eGFR ≥45 mL/min/1.73 m² for glycemic control 1, 2
• Dapagliflozin is not recommended for initiation when eGFR <45 mL/min/1.73 m² if the primary goal is glycemic control, as glucose-lowering efficacy is significantly reduced at lower eGFR levels 1, 2

For Cardiovascular and Renal Benefits

• Dapagliflozin can be initiated at 10 mg daily in patients with eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection 2, 3
• The DAPA-CKD trial demonstrated significant benefits in patients with eGFR between 25-75 mL/min/1.73 m² 1
• Dapagliflozin reduced the risk of kidney disease progression, end-stage kidney disease, and cardiovascular death in patients with CKD regardless of diabetes status 2, 3

Continuation Recommendations

• If eGFR falls below 25 mL/min/1.73 m² during treatment, dapagliflozin 10 mg daily may be continued for cardiovascular and renal benefits until dialysis initiation 2, 3
• The FDA label indicates that patients enrolled in the DAPA-CKD and DELIVER trials were not required to discontinue therapy if eGFR fell below 25 mL/min/1.73 m² or if dialysis was initiated 3
• The initial eGFR dip of 3-5 mL/min/1.73 m² in the first few weeks of therapy is expected and generally not a reason to discontinue therapy 4, 5

Evidence from Clinical Trials

• The DAPA-CKD trial included 4,304 participants with a mean eGFR of 43.1 ± 12.4 mL/min/1.73 m² (range 25-75 mL/min/1.73 m²) and demonstrated significant renal and cardiovascular benefits 1
• Dapagliflozin reduced the primary composite endpoint (≥50% sustained decline in eGFR, ESKD, or renal/CV death) by 39% (HR 0.61 [95% CI 0.51-0.72]) 1, 2
• The DAPA-HF trial showed that baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in heart failure with reduced ejection fraction 6
• The DELIVER trial demonstrated that dapagliflozin slowed the rate of eGFR decline compared with placebo in patients with heart failure with preserved ejection fraction, regardless of baseline kidney function 7

Monitoring and Safety Considerations

• Assess renal function prior to initiation and periodically thereafter 2, 4
• Evaluate volume status before starting dapagliflozin and correct volume depletion if present 2
• Temporarily withhold dapagliflozin for at least 3 days prior to major surgery or procedures requiring prolonged fasting 2
• Monitor for potential adverse effects including genital mycotic infections, urinary tract infections, volume depletion, and euglycemic diabetic ketoacidosis 2, 4

Clinical Practice Algorithm

1. Determine treatment goal:

   • For glycemic control only: Use dapagliflozin if eGFR ≥45 mL/min/1.73 m² 1, 2
   • For cardiovascular/renal protection: Use dapagliflozin if eGFR ≥25 mL/min/1.73 m² 2, 3

2. For patients with eGFR <25 mL/min/1.73 m²:

   • Do not initiate dapagliflozin 2, 3
   • Consider GLP-1 receptor agonists as preferred agents 1

3. For patients already on dapagliflozin:

   • Continue therapy even if eGFR falls below 25 mL/min/1.73 m² for cardiovascular and renal benefits until dialysis initiation 2, 3
   • Monitor renal function and volume status regularly 2, 4

4. Expect and manage initial eGFR dip:

   • An initial decrease in eGFR of 3-5 mL/min/1.73 m² is expected and usually returns toward baseline within weeks 4, 5
   • This initial dip does not predict worse long-term outcomes and may be associated with better long-term renal protection 5

The evidence clearly supports using dapagliflozin in patients with impaired renal function, with different thresholds depending on the treatment goal. For glycemic control, the cut-off is eGFR ≥45 mL/min/1.73 m², while for cardiovascular and renal protection, dapagliflozin can be initiated at eGFR levels as low as 25 mL/min/1.73 m².