Is Jardiance (Empagliflozin) suitable for patients with end-stage renal disease (ESRD) on dialysis?

Jardiance (Empagliflozin) is Not Appropriate for Dialysis Patients

Jardiance (empagliflozin) is contraindicated in patients on dialysis according to the FDA label and should not be used in this population.1

Rationale for Contraindication

Empagliflozin is specifically contraindicated in:

• Patients with severe renal impairment
• End-stage renal disease (ESRD)
• Patients receiving dialysis1

The FDA label clearly states that "JARDIANCE is not expected to be effective in these patient populations."1 This contraindication is based on both safety concerns and lack of efficacy in dialysis patients.

Mechanism of Action and Efficacy Considerations

Empagliflozin works by inhibiting sodium-glucose cotransporter-2 (SGLT2) in the proximal renal tubules, which:

• Reduces renal glucose reabsorption
• Increases urinary glucose excretion
• Lowers blood glucose levels

In patients on dialysis:

• The mechanism of action is rendered ineffective due to minimal remaining kidney function
• The urinary glucose excretion effect is negligible
• The glycemic benefits are essentially lost2

Safety Concerns in Dialysis Patients

Several safety concerns exist when considering SGLT2 inhibitors in dialysis patients:

1. Volume depletion risks: Dialysis patients already have compromised volume status and are at higher risk for hypotension1

2. Electrolyte abnormalities: Dialysis patients have altered electrolyte management that could be further complicated

3. Ketoacidosis risk: SGLT2 inhibitors can cause euglycemic ketoacidosis, which could be particularly dangerous in the dialysis population3

4. Medication burden: Dialysis patients typically have complex medication regimens, and adding medications with minimal benefit increases risk3

Evidence from Guidelines

The 2022 ADA/KDIGO consensus report on diabetes management in chronic kidney disease provides clear guidance on SGLT2 inhibitor use based on kidney function:

• For patients with eGFR ≥20 ml/min/1.73 m², SGLT2 inhibitors with proven kidney or cardiovascular benefit are recommended
• For patients on dialysis (eGFR <15 ml/min/1.73 m²), SGLT2 inhibitors are not recommended for initiation3

The FDA label for empagliflozin specifically states that it should not be initiated in patients with eGFR <45 ml/min/1.73 m² and should be discontinued if eGFR falls persistently below this threshold.1

Alternative Approaches for Dialysis Patients

For patients with diabetes on dialysis, alternative approaches include:

1. Insulin therapy: Insulin is the preferred treatment for patients with ESRD and diabetes mellitus requiring medication4

2. GLP-1 receptor agonists: Some GLP-1 receptor agonists like dulaglutide, liraglutide, and semaglutide do not require dose adjustment in ESRD and may be considered3

3. DPP-4 inhibitors: Linagliptin does not require dose adjustment in ESRD and can be considered3

Medication Reconciliation Importance

This case highlights the critical importance of medication reconciliation for dialysis patients:

• Medication reconciliation should be performed at each transition of care to prevent medication errors in ESRD patients3
• Many medications require dose adjustments or are contraindicated in ESRD3
• Dialysis patients are at high risk for medication-related problems due to altered pharmacokinetics

Conclusion

While empagliflozin has shown benefits in patients with chronic kidney disease with eGFR ≥20 ml/min/1.73 m² in studies like EMPA-KIDNEY5, these benefits do not extend to dialysis patients. The FDA label explicitly contraindicates Jardiance in patients on dialysis, and there is no evidence supporting its use in this population.