SGLT2 Inhibitors in Patients with Worsening Renal Function
SGLT2 inhibitors should be reduced in dose or discontinued in patients with severe renal impairment (eGFR <20 mL/min/1.73 m²), but can be safely initiated in patients with moderate renal impairment (eGFR ≥20 mL/min/1.73 m²) and continued even if eGFR subsequently falls below 20 mL/min/1.73 m² until kidney replacement therapy is initiated. 1
Dosing Considerations Based on Renal Function
eGFR Thresholds for Initiation and Continuation
- Initiation threshold: eGFR ≥20 mL/min/1.73 m² 1
- Continuation: Once initiated, SGLT2 inhibitors can be continued even if eGFR falls below 20 mL/min/1.73 m², unless not tolerated or kidney replacement therapy is started 1
Specific Agent Considerations
- Canagliflozin: Maximum 100 mg daily for eGFR 30-59 mL/min/1.73 m²; not recommended for initiation if eGFR <30 mL/min/1.73 m² 1
- Dapagliflozin: 10 mg daily for eGFR 30-44 mL/min/1.73 m²; not recommended for initiation if eGFR <25 mL/min/1.73 m² 1
- Empagliflozin: 10 mg daily for eGFR 30-44 mL/min/1.73 m²; not recommended for use if eGFR <45 mL/min/1.73 m² according to some guidelines 1
Expected eGFR Changes After Initiation
- A reversible decrease in eGFR of 3-5 mL/min/1.73 m² is common in the first 4 weeks after starting SGLT2 inhibitors 1
- This initial "eGFR dip" is generally not an indication to discontinue therapy 1
- eGFR typically stabilizes during ongoing therapy and may be protective against acute kidney injury in the long term 1
Monitoring Recommendations
- Monitor renal function at baseline before initiating therapy
- No need to alter the frequency of CKD monitoring after starting SGLT2 inhibitors 1
- Reassess volume status after drug initiation, especially in patients at risk for hypovolemia 1
Risk Mitigation Strategies
Volume Depletion
- Consider decreasing thiazide or loop diuretic dosages before starting SGLT2 inhibitors in patients at risk for hypovolemia 1
- Advise patients about symptoms of volume depletion and low blood pressure 1
- Patients with impaired renal function are at higher risk for volume depletion and hypotension 2
Ketoacidosis Risk
- Withhold SGLT2 inhibitors during:
- Times of prolonged fasting
- Surgery or critical medical illness
- Acute illness 1
- Monitor for ketoacidosis regardless of blood glucose levels, as "euglycemic ketoacidosis" can occur 1, 2
- Educate patients to discontinue SGLT2 inhibitors and seek medical attention if signs of ketoacidosis occur 2
Infection Risk
- Provide hygienic counseling to reduce risk of genital mycotic infections 1
- Monitor for signs of infection, especially in immunocompromised patients 1
Special Considerations
- SGLT2 inhibitors have not been adequately studied in kidney transplant recipients, who may be at increased risk for infections due to immunosuppression 1
- Elderly patients require special attention due to higher risk of renal impairment, orthostatic hypotension, and dehydration 3
- For patients with diabetes requiring insulin, maintain at least low-dose insulin when using SGLT2 inhibitors to reduce ketoacidosis risk 1
Potential Benefits Despite Reduced Renal Function
Despite reduced glucose-lowering efficacy in CKD, SGLT2 inhibitors may still provide important benefits:
- Reduction in cardiovascular events and mortality 1
- Decreased risk of heart failure hospitalizations 1
- Slowed progression of kidney disease 1
- Reduction in albuminuria 4, 5
By following these precautions and monitoring recommendations, SGLT2 inhibitors can be used safely and effectively in many patients with worsening renal function, providing important cardiorenal benefits beyond glycemic control.