SGLT2 Inhibitor Discontinuation Based on eGFR Criteria
SGLT2 inhibitors should be discontinued if eGFR falls persistently below 20 mL/min/1.73 m² or if kidney replacement therapy is initiated, but can be continued even if eGFR falls below the initial threshold for starting therapy. 1
Current Recommendations for SGLT2 Inhibitor Use Based on eGFR
Initiation Thresholds
- eGFR ≥ 20 mL/min/1.73 m²: SGLT2 inhibitors can be initiated 1
- eGFR < 20 mL/min/1.73 m²: Do not initiate SGLT2 inhibitors 1, 2
Continuation Thresholds
- 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 initiated 1, 2
- This recommendation is based on evidence showing continued cardiovascular and renal benefits even with declining kidney function 3
Drug-Specific Considerations
Different SGLT2 inhibitors have varying FDA-approved eGFR thresholds:
Empagliflozin (Jardiance)
- Do not initiate if eGFR < 45 mL/min/1.73 m²
- Discontinue if eGFR persistently < 45 mL/min/1.73 m² 4, 1
Dapagliflozin
- Avoid initiating if eGFR < 60 mL/min/1.73 m² for glycemic control
- Can be initiated at eGFR ≥ 25 mL/min/1.73 m² for heart failure and CKD indications 5
Canagliflozin
- Do not exceed 100 mg/day if eGFR 45-59 mL/min/1.73 m²
- Avoid use and discontinue if eGFR persistently < 45 mL/min/1.73 m² 1
Important Clinical Considerations
Expected Initial eGFR Decline
- SGLT2 inhibitors typically cause an acute, reversible decrease in eGFR of 3-5 mL/min/1.73 m² within the first 4 weeks of initiation
- This initial decline is hemodynamic and generally not a reason to discontinue therapy 2
Monitoring Recommendations
- Assess baseline renal function before initiating SGLT2 inhibitors
- Monitor eGFR periodically, especially in patients with moderate CKD
- More frequent monitoring when eGFR < 60 mL/min/1.73 m² 1, 2
Precautions and Management
- Consider reducing diuretic doses in patients at risk for volume depletion before starting SGLT2 inhibitors 2
- Temporarily withhold SGLT2 inhibitors during times of prolonged fasting, surgery, or critical medical illness 1
- Monitor for signs of volume depletion and hypotension after initiating therapy 2
Evidence for Continued Use with Low eGFR
Recent evidence supports the continuation of SGLT2 inhibitors even with declining kidney function:
- A 2023 study found that patients with heart failure who experienced deterioration of eGFR to < 25 mL/min/1.73 m² still benefited from continuation of dapagliflozin with no excess safety concerns 3
- A 2024 meta-analysis demonstrated that SGLT2 inhibitors significantly improved cardio-renal outcomes and were generally safe in CKD patients with eGFR < 30 mL/min/1.73 m² 6
Common Pitfalls to Avoid
Discontinuing too early: Stopping SGLT2 inhibitors solely due to the initial eGFR decline (3-5 mL/min/1.73 m²) that occurs within the first 4 weeks 2
Not adjusting concomitant medications: Failing to reduce doses of diuretics or insulin/sulfonylureas when starting SGLT2 inhibitors, increasing risk of volume depletion or hypoglycemia 2
Inconsistent monitoring: Not following up on kidney function after initiating SGLT2 inhibitors, especially in patients with baseline eGFR < 60 mL/min/1.73 m² 1
Clinical inertia: Hesitating to prescribe SGLT2 inhibitors to eligible patients with CKD - only about 33% of eligible patients currently receive these medications 7
The most recent evidence and guidelines support a more liberal approach to SGLT2 inhibitor continuation even as kidney function declines, recognizing their significant cardiovascular and renal benefits that extend beyond glycemic control.