Jardiance (Empagliflozin) in End-Stage Renal Disease
Jardiance (empagliflozin) is contraindicated in patients with end-stage renal disease (ESRD) or those on dialysis and should not be used in this population. 1
Contraindications and Renal Function
The FDA drug label for Jardiance explicitly states that it is contraindicated in:
- Patients with severe renal impairment
- End-stage renal disease (ESRD)
- Patients on dialysis 1
This contraindication exists because:
Efficacy concerns: Jardiance works by inhibiting SGLT2 in the renal proximal tubule to reduce glucose reabsorption. In ESRD, this mechanism becomes ineffective due to severely reduced kidney function.
Safety profile: The FDA label clearly states that "JARDIANCE is not expected to be effective in these patient populations" with severe renal impairment, ESRD, or those receiving dialysis 1.
Evidence from Clinical Guidelines
Current diabetes management guidelines support this contraindication:
The American Diabetes Association (ADA) guidelines note that while SGLT2 inhibitors like empagliflozin have shown benefits in patients with chronic kidney disease, these benefits were demonstrated in patients with eGFR ranges above those seen in ESRD 2.
Clinical trials evaluating empagliflozin's renal effects, such as EMPA-REG OUTCOME, included patients with mild to moderate renal impairment but not those with ESRD 2.
Pharmacokinetics in Renal Impairment
Research on empagliflozin pharmacokinetics shows:
While systemic exposure to empagliflozin increases with declining renal function (approximately 48% higher in ESRD compared to normal renal function), the critical issue is that urinary glucose excretion (UGE) - the mechanism by which empagliflozin works - decreases significantly with increasing renal impairment 3, 4.
In patients with severe renal impairment, UGE is markedly reduced, making the drug ineffective for its intended purpose 4.
Alternative Approaches for ESRD Patients
For patients with ESRD who need glycemic management:
- Other antihyperglycemic agents that don't rely on renal function for efficacy should be considered.
- GLP-1 receptor agonists may be an option for some ESRD patients, though individual agent prescribing information should be consulted.
- Insulin remains an important therapy for many patients with ESRD.
Clinical Implications
- Medication review: Patients progressing to ESRD who are currently on empagliflozin should have this medication discontinued.
- Monitoring: If a patient with advanced CKD (not yet ESRD) is on empagliflozin, regular monitoring of renal function is essential, with plans to discontinue the medication if they progress to ESRD.
- Risk management: Using empagliflozin in ESRD patients could expose them to potential adverse effects without therapeutic benefit.
In conclusion, while SGLT2 inhibitors like empagliflozin have shown significant cardiovascular and renal benefits in patients with type 2 diabetes and earlier stages of CKD, they are explicitly contraindicated in ESRD and should not be used in this patient population.