At what Glomerular Filtration Rate (GFR) do you hold Jardiance (Empagliflozin)?

Jardiance (Empagliflozin) Hold Threshold Based on GFR

Jardiance (empagliflozin) should not be initiated in patients with eGFR less than 45 mL/min/1.73 m² and should be discontinued if eGFR falls persistently below 45 mL/min/1.73 m². 1

FDA Labeling Requirements

• Empagliflozin should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m² 1
• No dose adjustment is needed in patients with an eGFR greater than or equal to 45 mL/min/1.73 m² 1
• Empagliflozin should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m² 1
• Assessment of renal function is recommended prior to initiation of empagliflozin and periodically thereafter 1

Recent Guideline Evolution

• Recent guidelines from ADA and KDIGO (2022) have updated recommendations to allow SGLT2 inhibitor initiation at lower eGFR thresholds than the FDA label indicates 2
• The KDIGO 2022 guideline recommends initiation of an SGLT2i for patients with T2D and CKD who have eGFR ≥20 ml/min/1.73 m² (updated from ≥30 ml/min/1.73 m² in the 2020 guideline) 2
• These changes are driven by findings from newer trials including DAPA-CKD and EMPEROR trials 2

Clinical Decision Algorithm

1. For patients with eGFR ≥45 mL/min/1.73 m²:

   • Initiate empagliflozin at standard dosing (10 mg once daily) 1
   • May increase to 25 mg once daily if tolerated 1

2. For patients with eGFR <45 mL/min/1.73 m²:

   • According to FDA labeling: Do not initiate empagliflozin 1
   • If patient is already on empagliflozin: Discontinue if eGFR persistently falls below 45 mL/min/1.73 m² 1
   • Consider alternative SGLT2 inhibitors with proven efficacy at lower eGFR (e.g., dapagliflozin) 2

3. For patients with eGFR 20-44 mL/min/1.73 m²:

   • Per recent KDIGO guidelines (not FDA labeling): May consider initiating an SGLT2i with proven kidney or cardiovascular benefit 2
   • Strongest evidence for initiation in this range exists for patients with concomitant albuminuria or heart failure 2

Important Considerations and Monitoring

• Glucose-lowering efficacy of SGLT2 inhibitors decreases with declining renal function, but kidney and cardiovascular benefits may be preserved 2, 3
• Monitor for volume depletion, especially in patients with renal impairment 1
• Implement risk mitigation strategies for potential side effects including genital mycotic infections and ketoacidosis 2
• Once initiated, SGLT2 inhibitors can be continued at lower levels of eGFR according to recent guidelines 2

Clinical Pearls and Caveats

• The initial eGFR dip of 3-5 mL/min/1.73 m² in the first 4 weeks of therapy is expected and generally not a reason to discontinue therapy 2
• SGLT2 inhibitors have been observed to have consistent efficacy and safety across studied ranges of eGFR 2
• Recent clinical trials (EMPA-KIDNEY) have shown benefits in patients with chronic kidney disease regardless of primary kidney disease etiology 4
• The discrepancy between FDA labeling (hold at eGFR <45) and newer guidelines (may initiate at eGFR ≥20) reflects the rapid evolution of evidence in this area 2