Is there a role for Dapagliflozin (Forxiga) in patients with Impaired renal function on dialysis?

Dapagliflozin in Patients on Dialysis

There is currently insufficient evidence to recommend dapagliflozin for patients on dialysis, and it should not be used in this population due to lack of proven efficacy and safety data. 1

Current Evidence and Recommendations

• The KDOQI Work Group states that there is not enough evidence to suggest that SGLT2 inhibitors like dapagliflozin are effective in patients receiving kidney replacement therapy 1
• While the FDA has removed the statement that dapagliflozin should be discontinued when dialysis is initiated, this was based on limited safety data from patients who initiated dialysis during the DAPA-CKD trial, not on evidence of efficacy 1
• Dapagliflozin is currently recommended for patients with eGFR ≥20 mL/min/1.73 m², but not for those on dialysis 1

Pharmacokinetic Considerations

• A recent pharmacokinetic study showed that in patients with kidney failure on dialysis, dapagliflozin was slightly dialyzable with only 0.10% of the administered dose recovered from dialysate 2
• The same study found that dapagliflozin had a slightly higher peak concentration (Cmax) in kidney failure patients (117 ng/ml) compared to controls (97.6 ng/ml) 2
• Dapagliflozin accumulation was higher in kidney failure patients (26.7%) compared to controls (9.5%), suggesting potential for drug accumulation with repeated dosing 2

Mechanism of Action and Efficacy Concerns

• SGLT2 inhibitors like dapagliflozin work by inhibiting glucose reabsorption in the proximal tubule of the kidney, which requires functioning nephrons 3
• Pharmacodynamic effects of dapagliflozin are significantly attenuated with declining kidney function - renal glucose clearance is reduced by 84% in patients with severe renal impairment compared to those with normal renal function 3
• The glucose-lowering efficacy of dapagliflozin decreases substantially with declining renal function, making it ineffective for glycemic control in patients with eGFR <45 mL/min/1.73 m² 4

Safety Considerations

• While the single pharmacokinetic study reported no serious adverse events in dialysis patients receiving dapagliflozin 2, this is insufficient evidence to establish long-term safety
• Potential risks in dialysis patients include:
  • Volume depletion, which could be particularly problematic in dialysis patients who already have fluid management challenges 5
  • Diabetic ketoacidosis, which can occur with SGLT2 inhibitors and may present with blood glucose levels lower than typically expected 5
  • Genital mycotic infections and urinary tract infections, which are common adverse effects of SGLT2 inhibitors 4

Ongoing Research

• The KDOQI guidelines note that ongoing trials are exploring the potential benefits of SGLT2 inhibitors in dialysis and transplant patients 1
• Until these trials are completed and provide clear evidence of safety and efficacy, dapagliflozin should not be used in dialysis patients 1

Clinical Approach

• For patients with CKD who are not yet on dialysis:
  • Dapagliflozin can be initiated in patients with eGFR ≥20 mL/min/1.73 m² 1
  • If a patient on dapagliflozin initiates dialysis, the current evidence does not support continuing the medication 1
• For patients already on dialysis:
  • Do not initiate dapagliflozin due to lack of evidence for efficacy and safety 1
  • Consider alternative evidence-based therapies for cardiovascular risk reduction in dialysis patients 1