Farxiga for Kidney Protection in Type 2 Diabetes
Yes, Farxiga (dapagliflozin) provides robust kidney protection in patients with type 2 diabetes and should be used specifically for this indication, particularly in those with chronic kidney disease (CKD) characterized by eGFR 25-75 mL/min/1.73 m² and/or albuminuria (UACR >30 mg/g, especially >300 mg/g). 1
Primary Renal Protection Evidence
The DAPA-CKD trial demonstrated definitive kidney protection with dapagliflozin 10 mg daily, showing a 39% reduction (HR 0.61; 95% CI 0.51-0.72) in the composite outcome of sustained decline in eGFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes over 2.4 years. 1 This benefit was observed in patients with CKD (UACR 200-5,000 mg/g and eGFR 25-75 mL/min/1.73 m²), both with and without diabetes. 1
For the renal-specific composite outcome (sustained decline in eGFR ≥50%, end-stage kidney disease, or renal death), dapagliflozin reduced risk by 44% (HR 0.56; 95% CI 0.45-0.68). 1
Guideline-Based Recommendations for Use
The American Diabetes Association and European Association for the Study of Diabetes provide clear guidance on when to use SGLT2 inhibitors like dapagliflozin for kidney protection: 1
- Patients with type 2 diabetes and CKD with UACR >300 mg/g and eGFR 30-90 mL/min/1.73 m² have the strongest evidence for benefit 1
- Patients with eGFR 30 to ≤60 mL/min/1.73 m² or UACR >30 mg/g should be considered for SGLT2 inhibitor therapy 1
- The decision to use dapagliflozin for kidney protection should be made independently of baseline HbA1c or glycemic targets 1
Additional Cardiovascular and Renal Benefits
Beyond primary kidney protection, dapagliflozin demonstrated:
- 47% reduction in composite renal events (HR 0.53; 95% CI 0.43-0.66) in the DECLARE-TIMI 58 trial 2
- 17% reduction in cardiovascular death or hospitalization for heart failure (HR 0.83; 95% CI 0.73-0.95) 1, 2
- 27% reduction in hospitalization for heart failure alone (HR 0.73; 95% CI 0.61-0.88) 2
These benefits extend across the spectrum of cardiovascular risk, including patients without established atherosclerotic cardiovascular disease but with multiple risk factors. 1
FDA-Approved Indications
The FDA specifically approves dapagliflozin to reduce the risk of further worsening of kidney disease, end-stage kidney disease (ESKD), death due to cardiovascular disease, and hospitalization for heart failure in adults with chronic kidney disease. 3 This indication is independent of diabetes status, as the DAPA-CKD trial included patients both with and without diabetes. 1
Practical Implementation
Start dapagliflozin 10 mg once daily in patients with: 3
- Type 2 diabetes with eGFR ≥25 mL/min/1.73 m² and evidence of kidney disease (albuminuria or reduced eGFR)
- Maximized renin-angiotensin system blockade (ACE inhibitor or ARB at maximum tolerated dose) 1
Do not use dapagliflozin in: 3
- Patients with eGFR <25 mL/min/1.73 m² (not studied and unlikely to be effective)
- Certain genetic forms of polycystic kidney disease
- Patients taking or recently receiving immunosuppressive therapy for kidney disease
Safety Considerations for Kidney Protection Use
Monitor for volume depletion, particularly in patients: 3
- Taking diuretics or antihypertensive medications
- Age ≥65 years
- With baseline eGFR 30-60 mL/min/1.73 m²
- On low-salt diets
The risk of acute kidney injury, volume depletion, and amputations did not differ with dapagliflozin compared to placebo across all levels of kidney function in DECLARE-TIMI 58. 4
Common adverse effects include genital mycotic infections (particularly in women) and urinary tract infections, but these do not outweigh the substantial mortality and morbidity benefits. 3, 5
Comparison to Other SGLT2 Inhibitors
While canagliflozin also demonstrated kidney protection in the CREDENCE trial (40% reduction in CKD progression), canagliflozin carries a 97% increased risk of lower-limb amputation (HR 1.97; 95% CI 1.41-2.75) and increased fracture risk, making dapagliflozin a safer choice for most patients. 6 Empagliflozin reduced CKD progression by 39% but has less extensive kidney-specific trial data compared to dapagliflozin's DAPA-CKD trial. 6
The kidney protective effects of dapagliflozin are independent of its glucose-lowering effects, as demonstrated by consistent benefits in patients with and without diabetes and across all HbA1c levels. 1