Jardiance (Empagliflozin) in Stage 4 Chronic Kidney Disease
Jardiance (empagliflozin) is contraindicated in patients with stage 4 chronic kidney disease (eGFR <30 mL/min/1.73 m²) and should not be initiated in patients with eGFR less than 45 mL/min/1.73 m². 1
FDA Labeling and Contraindications
- The FDA label for Jardiance (empagliflozin) clearly states that it should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m² 1
- Jardiance should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m² 1
- Severe renal impairment, end-stage renal disease, or dialysis are listed as contraindications for Jardiance 1
Mechanism and Efficacy Considerations
- SGLT2 inhibitors like empagliflozin work by preventing glucose reabsorption in the proximal tubule of the kidney, which reduces their efficacy in advanced kidney disease 2
- At low eGFR levels (stage 4 CKD), the glycemic efficacy of empagliflozin is significantly attenuated due to reduced filtration of glucose 2
- The FDA label recommendation is based on both reduced efficacy and safety concerns in advanced kidney disease 1
Recent Clinical Evidence
- While recent trials have explored SGLT2 inhibitors in CKD patients, most studies have focused on dapagliflozin rather than empagliflozin for patients with very low eGFR 3
- The EMPA-KIDNEY trial included patients with eGFR as low as 20 mL/min/1.73 m², but this data is more recent than the current FDA labeling 4
- The DAPA-CKD trial showed that dapagliflozin may be effective in stage 4 CKD patients with a 27% reduction in the primary composite endpoint, but this evidence is specific to dapagliflozin, not empagliflozin 3
Safety Considerations
- Empagliflozin can cause intravascular volume contraction, which poses increased risks in patients with renal impairment 1
- Risk of adverse events including hypotension is higher in patients with reduced renal function 1
- Ketoacidosis is a serious potential adverse effect of SGLT2 inhibitors, and the risk may be higher in patients with severely reduced kidney function 1
Alternative Medications for Stage 4 CKD
- Several diabetes medications can be used safely in stage 4 CKD with appropriate dose adjustments 2:
- DPP-4 inhibitors: Linagliptin requires no dose adjustment; sitagliptin, saxagliptin, and alogliptin can be used with dose reductions 2
- GLP-1 receptor agonists: Liraglutide, dulaglutide, and semaglutide can be used without dose adjustment in CKD stage 4 2
- Insulin: Can be used with dose adjustment and careful monitoring for hypoglycemia 2
Conclusion
Based on current FDA labeling and guidelines, empagliflozin (Jardiance) is contraindicated in stage 4 CKD (eGFR <30 mL/min/1.73 m²) and should not be initiated in patients with eGFR <45 mL/min/1.73 m². While emerging research suggests potential benefits of some SGLT2 inhibitors in advanced CKD, the official recommendation remains to avoid empagliflozin in this patient population until FDA labeling is updated to reflect newer evidence.