CKD Stage 3B Patients Should Not Be on Saxagliptin, but Dapagliflozin Is Recommended
Patients with CKD stage 3B should not be on saxagliptin but can benefit from dapagliflozin therapy for renal and cardiovascular protection, even with eGFR as low as 20 mL/min/1.73m².
Saxagliptin in CKD Stage 3B
Saxagliptin is specifically contraindicated in patients with heart failure risk and CKD:
- The 2020 European Society of Cardiology (ESC) guidelines explicitly state that "saxagliptin is not recommended in patients with T2DM and a high risk of HF" 1
- Saxagliptin is also not recommended in patients with heart failure, as stated in the 2022 Diabetes Care guidelines 1
- CKD patients have inherently higher cardiovascular risk, making saxagliptin particularly problematic for this population
Dapagliflozin in CKD Stage 3B
Dapagliflozin is beneficial in CKD stage 3B (eGFR 30-44 mL/min/1.73m²):
- The 2023 Diabetes Care guidelines recommend SGLT2 inhibitors like dapagliflozin for patients with eGFR ≥20 mL/min/1.73m² to reduce CKD progression and cardiovascular events 1
- FDA labeling for dapagliflozin states it can be initiated in patients with eGFR ≥25 mL/min/1.73m² and continued even if eGFR falls below 25 mL/min/1.73m² 2
- The DAPA-CKD trial demonstrated significant benefits with dapagliflozin in CKD patients, showing a 39% reduction in the primary composite outcome (HR 0.61 [95% CI 0.51-0.72]) 2
Benefits of Dapagliflozin in CKD
Dapagliflozin provides multiple benefits for CKD patients:
- Reduces risk of sustained eGFR decline by 44% (HR 0.56 [95% CI 0.45-0.68]) 2
- Decreases hospitalization for heart failure (HR 0.51 [95% CI 0.34-0.76]) 2
- Reduces all-cause mortality by 31% (HR 0.69 [95% CI 0.53-0.88]) 2
- Benefits persist regardless of diabetes status 3
- Effective across various CKD etiologies including diabetic nephropathy, glomerulonephritides, and hypertensive kidney disease 3
Dosing Considerations
For CKD stage 3B patients:
- Dapagliflozin: Use 10 mg once daily for renal and cardiovascular protection 2
- Note that while dapagliflozin's glucose-lowering effect is reduced at eGFR <45 mL/min/1.73m², its cardiovascular and renal benefits persist 4
- Dapagliflozin can be initiated with eGFR as low as 25 mL/min/1.73m² and continued even if eGFR falls below this threshold 2
Safety Considerations
When using dapagliflozin in CKD stage 3B:
- Monitor for volume depletion, especially when combined with diuretics 4
- Watch for genital mycotic infections (more common in women) 4
- Be vigilant for diabetic ketoacidosis, particularly in insulin-deficient patients 4
- The DAPA-CKD trial showed similar rates of serious adverse events between dapagliflozin and placebo groups, indicating good tolerability 3
- Dapagliflozin's safety profile remains consistent regardless of concomitant cardiovascular medications 5
Conclusion
For CKD stage 3B patients, dapagliflozin provides significant renal and cardiovascular protection with an acceptable safety profile, while saxagliptin should be avoided due to increased heart failure risk. The combination therapy of these two medications is not recommended due to the contraindication of saxagliptin in this population.