SGLT2 Inhibitors for CKD Patients Without Diabetes: Dapagliflozin is the Best Choice
For patients with chronic kidney disease (CKD) without diabetes, dapagliflozin is the best SGLT2 inhibitor based on the strongest evidence from dedicated kidney outcome trials. 1, 2
Evidence Supporting SGLT2 Inhibitors in Non-Diabetic CKD
Efficacy in Non-Diabetic CKD
- SGLT2 inhibitors are now recommended for CKD patients regardless of diabetes status, with strong evidence supporting their use in non-diabetic CKD patients 1
- The 2024 KDIGO guidelines provide a strong recommendation (1A) for SGLT2 inhibitors in adults with CKD having eGFR ≥20 mL/min/1.73 m² with urine albumin-to-creatinine ratio (ACR) ≥200 mg/g, or heart failure, irrespective of albuminuria 1
- For adults with eGFR 20-45 mL/min/1.73 m² with urine ACR <200 mg/g, SGLT2 inhibitors are suggested with a 2B recommendation 1
Risk Stratification Approach
- The 2024 BMJ clinical practice guideline recommends SGLT2 inhibitors based on risk stratification 1:
- Strong recommendation for patients at high and very high risk of CKD progression
- Weak recommendation for patients at low and moderate risk of CKD progression
- Benefits are consistent in patients with and without diabetes across all risk categories 1, 2
Comparing Available SGLT2 Inhibitors for Non-Diabetic CKD
Dapagliflozin
- Dapagliflozin has the strongest evidence specifically in non-diabetic CKD from the DAPA-CKD trial, which included patients with and without diabetes 2, 3
- DAPA-CKD showed dapagliflozin reduced the primary composite endpoint (≥50% eGFR decline, end-stage kidney disease, or renal/CV death) with HR 0.61 (95% CI 0.51-0.72) 2
- Dapagliflozin is the first SGLT2 inhibitor to demonstrate reduced all-cause mortality in CKD patients with HR 0.69 (95% CI 0.53-0.88), with benefits consistent in both diabetic and non-diabetic patients 4, 2
- Dapagliflozin has a first-in-class indication specifically for CKD management 3
Empagliflozin
- Empagliflozin has evidence from the EMPA-KIDNEY trial (which was stopped early for efficacy) 5
- Can be initiated with eGFR >30 mL/min/1.73 m² according to FDA labeling, though clinical trials included participants with lower eGFR 1, 6
- Has demonstrated cardiovascular benefits in patients with heart failure regardless of diabetes status 2
Canagliflozin
- Canagliflozin has strong evidence primarily from the CREDENCE trial, which focused on diabetic kidney disease 4, 3
- Can be started with eGFR as low as 30 mL/min/1.73 m² per FDA labeling 7
- Has less specific evidence in non-diabetic CKD compared to dapagliflozin 2, 3
Practical Considerations for SGLT2 Inhibitor Use in CKD
Dosing and eGFR Thresholds
- Initiate SGLT2 inhibitors when eGFR ≥20 mL/min/1.73 m² 1
- Once initiated, it is reasonable to continue SGLT2 inhibitors even if eGFR falls below 20 mL/min/1.73 m², unless not tolerated or kidney replacement therapy is initiated 1
- Use the lowest effective dose from clinical trials 5
Monitoring and Expected Effects
- An initial, reversible decrease in eGFR of 3-5 mL/min/1.73 m² is expected within the first 4 weeks of therapy and is not a reason to discontinue 1, 3
- SGLT2 inhibitor initiation does not necessitate alteration of CKD monitoring frequency 1
Safety Considerations
- Withhold SGLT2 inhibitors during times of prolonged fasting, surgery, or critical medical illness due to increased risk of ketosis 1
- Monitor for potential adverse effects including genital mycotic infections, urinary tract infections, and volume depletion 1, 3
- SGLT2 inhibitors may reduce risk of hyperkalemia without causing hypokalemia, which can facilitate use of other kidney-protective therapies 3
Conclusion
Based on the strongest and most recent evidence, dapagliflozin is the best SGLT2 inhibitor for CKD patients without diabetes due to:
- Specific evidence from the DAPA-CKD trial showing benefits in non-diabetic CKD
- Demonstrated reduction in all-cause mortality
- First-in-class indication specifically for CKD management
- Consistent benefits across both diabetic and non-diabetic populations