Should Jardiance (Empagliflozin) be discontinued in patients with severe impaired renal function, specifically an estimated creatinine clearance of 15?

Discontinuation of Jardiance (Empagliflozin) at Creatinine Clearance of 15

Yes, Jardiance (empagliflozin) should be discontinued in patients with an estimated creatinine clearance of 15 mL/min. 1

Rationale for Discontinuation

• Jardiance is contraindicated in patients with severe renal impairment, end-stage renal disease, or dialysis according to the FDA label 1
• The drug should not be initiated in patients with eGFR less than 45 mL/min/1.73 m² and should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m² 1
• A creatinine clearance of 15 mL/min falls well below this threshold and is classified as severe renal dysfunction (CKD stage 4-5) 2

Classification of Renal Function

• Creatinine clearance of 15 mL/min corresponds to CKD stage 5 (kidney failure), which is defined as GFR <15 mL/min/1.73 m² 2
• This level of renal function typically requires consideration of renal replacement therapy (dialysis or kidney transplantation) 2

SGLT2 Inhibitors and Renal Function

• SGLT2 inhibitors like empagliflozin are not expected to be effective for glycemic control in advanced CKD 2
• The FDA label specifically states that empagliflozin should be discontinued in patients with eGFR persistently below 45 mL/min/1.73 m² 1
• The mechanism of action of SGLT2 inhibitors depends on adequate renal filtration, which is severely compromised at this level of kidney function 2

Safety Considerations

• At very low creatinine clearance levels, there is increased risk of adverse effects including:
  • Volume depletion and hypotension 1
  • Reduced drug clearance potentially leading to drug accumulation 2
  • Electrolyte abnormalities 2

Recent Research Developments

• While the EMPA-KIDNEY trial (2023) included some patients with eGFR as low as 20 mL/min/1.73 m², it did not specifically address safety and efficacy at the 15 mL/min level 3
• The study showed renal benefits in patients with CKD, but the FDA labeling has not yet been updated to reflect potential use at very low GFR levels 3, 4

Alternative Medications for Diabetes in Severe Renal Impairment

• For patients with severe renal impairment requiring antidiabetic therapy, consider:
  • Insulin (with dose adjustment) 2
  • DPP-4 inhibitors with appropriate dose adjustments (e.g., linagliptin requires no dose adjustment) 2
  • GLP-1 receptor agonists like liraglutide or dulaglutide which require no dose adjustment in severe renal impairment 2

Common Pitfalls to Avoid

• Continuing SGLT2 inhibitors in severe renal impairment based on potential renoprotective effects without considering the safety risks 2
• Failing to regularly monitor renal function in patients on empagliflozin, which could lead to continued use despite declining kidney function 1
• Not recognizing that the glycemic efficacy of SGLT2 inhibitors is significantly reduced at low GFR levels, potentially leading to inadequate diabetes control 2

In conclusion, based on the current FDA labeling and clinical guidelines, Jardiance should be discontinued when creatinine clearance reaches 15 mL/min, and alternative antidiabetic medications should be considered for glycemic management. 1, 2