Guidelines for Using Empagliflozin in Patients with Impaired Renal Function
Empagliflozin can be initiated in patients with eGFR ≥20 mL/min/1.73 m² for cardiovascular and renal benefits, despite FDA labeling recommending against use below eGFR 45 mL/min/1.73 m².
Renal Function Thresholds for Empagliflozin Use
- According to the FDA label, empagliflozin (Jardiance) should not be initiated in patients with eGFR less than 45 mL/min/1.73 m² and should be discontinued if eGFR is persistently below this threshold 1
- However, updated clinical guidelines from ADA/KDIGO (2022) recommend that SGLT2 inhibitors, including empagliflozin, can be initiated in patients with type 2 diabetes and chronic kidney disease with eGFR ≥20 mL/min/1.73 m² 2
- The strongest evidence for initiation in patients with eGFR 20-45 mL/min/1.73 m² is for those with concomitant albuminuria or heart failure 2, 3
- Empagliflozin is contraindicated in patients with severe renal impairment, end-stage renal disease, or on dialysis 1
Efficacy Considerations Across GFR Ranges
- Glucose-lowering efficacy of empagliflozin decreases substantially with declining renal function, making it less effective for glycemic control in patients with eGFR <45 mL/min/1.73 m² 2, 3
- Despite reduced glycemic efficacy, cardiovascular and renal benefits are preserved at lower eGFR levels 2, 4
- In the EMPEROR-Reduced trial, empagliflozin showed consistent benefits on heart failure outcomes across a broad range of baseline kidney function, including patients with eGFR as low as 20 mL/min/1.73 m² 4
- Empagliflozin reduced the risk of the composite kidney outcome (sustained decline in eGFR, chronic dialysis, or transplant) similarly in patients with and without CKD 4
Monitoring and Management
- Assess renal function prior to initiation of empagliflozin and periodically thereafter 1
- Expect an initial eGFR dip of 3-5 mL/min/1.73 m² in the first 4 weeks of therapy, which is generally not a reason to discontinue therapy 3
- Monitor for signs and symptoms of hypotension after initiating therapy, particularly in patients with renal impairment, the elderly, patients with low systolic blood pressure, and those on diuretics 1
- Correct volume depletion prior to initiation of empagliflozin 1
- Consider pausing empagliflozin during periods of acute illness or stressors to mitigate the risk of euglycemic ketoacidosis 2
Safety Considerations
- Empagliflozin causes intravascular volume contraction, which may lead to symptomatic hypotension, particularly in patients with renal impairment 1
- Risk of genital mycotic infections is increased with SGLT2 inhibitors; daily hygienic measures may reduce this risk 2
- Monitor for euglycemic ketoacidosis, which may occur with minimal to no elevation in blood glucose 2
- In patients requiring insulin, maintain at least low-dose insulin when using empagliflozin to reduce ketoacidosis risk 2
Continuation of Therapy
- According to the DAPA-CKD and CREDENCE trial protocols, SGLT2 inhibitors can be continued even if eGFR falls below initiation thresholds 2
- It is reasonable to continue therapy if eGFR falls below initiation thresholds unless the patient is not tolerating treatment or kidney replacement therapy is initiated 2
- The EMPEROR-Reduced trial demonstrated that empagliflozin was well tolerated in patients with CKD 4
Practical Approach to Empagliflozin Use Based on eGFR
- eGFR ≥45 mL/min/1.73 m²: Initiate empagliflozin for both glycemic control and cardio-renal benefits 1
- eGFR 20-45 mL/min/1.73 m²: Consider initiating empagliflozin for cardio-renal benefits, especially in patients with albuminuria or heart failure, but not for glycemic control 2, 4
- eGFR <20 mL/min/1.73 m² or dialysis: Do not use empagliflozin 1
By following these guidelines, clinicians can appropriately utilize empagliflozin across the spectrum of renal function to optimize cardiovascular and renal outcomes while minimizing risks.