Empagliflozin (Jardiance) Dosing in Chronic Kidney Disease
Empagliflozin (Jardiance) should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m² and should be discontinued if eGFR is persistently below this threshold, according to the FDA label. 1
Dosing Recommendations Based on Renal Function
For Patients with eGFR ≥45 mL/min/1.73 m²:
- Starting dose: 10 mg once daily in the morning, with or without food
- May increase to 25 mg once daily if tolerated well 1
- No dose adjustment needed in this eGFR range
For Patients with eGFR <45 mL/min/1.73 m²:
- Do not initiate empagliflozin therapy
- Discontinue empagliflozin if eGFR falls persistently below 45 mL/min/1.73 m² 1
For Patients with Severe Renal Impairment:
- Contraindicated in severe renal impairment, end-stage renal disease, or dialysis 1
Important Clinical Considerations
Pre-Initiation Assessment:
- Assess renal function before starting empagliflozin
- Evaluate for volume depletion and correct if present before initiation 1
- Consider potential for hypotension, especially in elderly patients or those on diuretics
Monitoring:
- Periodically assess renal function after initiation
- Monitor for signs and symptoms of hypotension
- Be vigilant for ketoacidosis, even at lower blood glucose levels 1
Evidence and Guideline Discrepancies
It's important to note that there is a discrepancy between the FDA label and recent clinical guidelines:
The FDA label (which takes precedence) states empagliflozin should not be initiated if eGFR <45 mL/min/1.73 m² 1
However, recent clinical guidelines from the American Diabetes Association (2024-2025) suggest SGLT2 inhibitors can be initiated if eGFR is above 20 mL/min/1.73 m² for kidney and heart failure protection, even though glucose-lowering efficacy diminishes at lower eGFR levels 2, 3
This discrepancy exists because newer evidence from the EMPA-KIDNEY trial demonstrated benefits of empagliflozin in patients with eGFR as low as 20 mL/min/1.73 m² 4, showing a 28% reduction in the risk of kidney disease progression or cardiovascular death compared to placebo.
Clinical Pitfalls to Avoid
- Do not rely solely on empagliflozin's glucose-lowering effect in advanced CKD, as this diminishes with declining kidney function
- Do not initiate in patients with severe volume depletion
- Be aware of increased risk for hypotension, especially in elderly patients or those on diuretics
- Monitor for euglycemic diabetic ketoacidosis, which can occur even with normal blood glucose levels
- Consider adjusting other glucose-lowering medications to prevent hypoglycemia when using empagliflozin in CKD 3
While recent clinical evidence suggests benefits at lower eGFR levels, clinicians should adhere to the FDA-approved dosing guidelines until the label is updated to reflect newer evidence.