At what Chronic Kidney Disease (CKD) grade is Empagliflozin (Empagliflozin) contraindicated?

Empagliflozin Contraindication Based on CKD Grade

Empagliflozin is contraindicated in patients with severe renal impairment (eGFR <20 mL/min/1.73 m²), end-stage renal disease (ESRD), or patients on dialysis. 1

Current Recommendations for Empagliflozin Use in CKD

The FDA drug label explicitly states that empagliflozin is contraindicated in:

• Severe renal impairment (eGFR <20 mL/min/1.73 m²)
• End-stage renal disease
• Patients on dialysis 1

This represents a significant evolution in guidance, as earlier recommendations were more restrictive:

• In 2019, SGLT2 inhibitors as a class were contraindicated with eGFR <30 mL/min/1.73 m² 2
• By 2022, the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) consensus report expanded use to eGFR ≥20 mL/min/1.73 m² 2

Evidence Supporting Current Recommendations

The expansion of empagliflozin use to patients with eGFR as low as 20 mL/min/1.73 m² is supported by:

1. The EMPEROR-Reduced trial, which demonstrated cardiovascular and kidney benefits in heart failure patients with eGFR as low as 20 mL/min/1.73 m² 3

2. The 2024 ADA Standards of Care, which recommends SGLT2 inhibitors for people with eGFR ≥20 mL/min/1.73 m² and type 2 diabetes, as they slow CKD progression and reduce heart failure risk independent of glucose management 2

Important Considerations for Use in CKD

• Efficacy changes: The glucose-lowering effect of empagliflozin diminishes with declining kidney function, but cardiorenal protective benefits persist 2

• Continuation below initiation threshold: Once initiated, empagliflozin can be continued at lower levels of eGFR until dialysis is initiated 2

• Monitoring: While using empagliflozin in patients with CKD:

  • Watch for volume depletion
  • Monitor for euglycemic diabetic ketoacidosis
  • Consider adjusting other glucose-lowering medications to prevent hypoglycemia
  • Educate about genital mycotic infections 2

Practical Application

For patients with type 2 diabetes and CKD:

1. eGFR ≥20 mL/min/1.73 m²: Empagliflozin can be initiated and continued
2. eGFR <20 mL/min/1.73 m²: Empagliflozin is contraindicated
3. Dialysis patients: Empagliflozin is contraindicated

Common Pitfalls to Avoid

• Outdated guidance: Earlier recommendations were more restrictive (contraindicated at eGFR <30 mL/min/1.73 m²). Current evidence supports use down to eGFR ≥20 mL/min/1.73 m²

• Confusing initiation vs. continuation thresholds: While initiation requires eGFR ≥20 mL/min/1.73 m², once started, empagliflozin can be continued at lower eGFR levels until dialysis

• Overlooking non-glycemic benefits: Even when glucose-lowering efficacy is reduced in advanced CKD, cardiovascular and kidney protective benefits persist

This guidance represents a significant evolution in the use of empagliflozin in CKD, with the most recent evidence supporting broader use in patients with reduced kidney function than previously recommended.