Is Farxiga (dapagliflozin) nephrotoxic?

Is Farxiga (Dapagliflozin) Nephrotoxic?

Farxiga (dapagliflozin) is not nephrotoxic; on the contrary, it provides significant renal protection and is approved for reducing the risk of kidney disease progression in patients with chronic kidney disease. 1, 2

Renal Effects of Dapagliflozin

Renal Protection

• Dapagliflozin has demonstrated significant renal protective effects in clinical trials:
  • In the DAPA-CKD trial, dapagliflozin reduced the risk of the primary composite renal endpoint by 39% (HR 0.61 [95% CI 0.51-0.72]) 2
  • The renal composite outcome (excluding cardiovascular death) was reduced by 44% (HR 0.56 [95% CI 0.45-0.68]) 1
  • These benefits were observed regardless of whether patients had type 2 diabetes 2

Initial eGFR Changes

• Dapagliflozin may cause a mild, initial decrease in eGFR during the first year of use 3
• This initial decrease is hemodynamic in nature and typically stabilizes or reverses with continued treatment
• Long-term data shows that dapagliflozin actually slows the decline in eGFR over time 1

FDA Approval for Kidney Protection

Dapagliflozin received FDA approval specifically for:

• Reducing the risk of sustained eGFR decline
• Reducing end-stage kidney disease
• Reducing cardiovascular death
• Reducing hospitalization for heart failure in adults with chronic kidney disease 1, 4

Dosing and Renal Function Considerations

Recommended Use Based on Renal Function

• For glycemic control in type 2 diabetes:
  • Not recommended for patients with eGFR <45 mL/min/1.73m² 3, 5
• For heart failure or CKD indications:
  • Can be used with eGFR as low as 25 mL/min/1.73m² 3, 5
  • If eGFR falls below 25 mL/min/1.73m², initiation is not recommended but continuation may be appropriate in patients with established heart failure or CKD 3
  • Contraindicated in patients on dialysis 3

Monitoring Recommendations

• Assess renal function prior to initiating dapagliflozin
• Monitor renal function periodically during treatment
• More frequent monitoring is advised in elderly patients and those with impaired renal function 5

Mechanism of Action

Dapagliflozin works by:

• Inhibiting SGLT2 in the proximal renal tubules, reducing glucose reabsorption 1
• Reducing sodium reabsorption and increasing sodium delivery to the distal tubule 1
• Decreasing intraglomerular pressure through tubuloglomerular feedback mechanisms 1
• These effects contribute to its renal protective properties rather than causing nephrotoxicity

Clinical Implications

• Dapagliflozin is beneficial for patients with CKD with eGFR ≥25 mL/min/1.73m² 3, 2
• The DAPA-CKD trial showed benefits in patients with albuminuria (UACR between 200 and 5000 mg/g) 1
• Benefits were consistent across various subgroups, including patients with and without type 2 diabetes 6
• Dapagliflozin should be continued as long as tolerated, even if eGFR falls below 20 mL/min/1.73m², until kidney replacement therapy is initiated 5

Conclusion

Rather than being nephrotoxic, dapagliflozin has proven renal protective effects and is specifically approved for reducing kidney disease progression. The initial small decrease in eGFR is a hemodynamic effect that stabilizes over time, and long-term use is associated with preservation of kidney function compared to placebo.