At what estimated Glomerular Filtration Rate (eGFR) are Sodium-Glucose Cotransporter 2 (SGTL2) inhibitors, such as Dapagliflozin (Forxiga), considered safe?

Safety of Dapagliflozin (SGLT2 Inhibitor) Based on eGFR Thresholds

Dapagliflozin can be safely initiated in patients with eGFR ≥25 mL/min/1.73 m² and can be continued even if eGFR falls below this threshold for kidney and cardiovascular benefits until dialysis is initiated. 1

Initiation Guidelines Based on eGFR

• For patients with eGFR ≥45 mL/min/1.73 m², dapagliflozin 10 mg daily can be initiated without dose adjustment for glycemic control 1
• For patients with eGFR 25-45 mL/min/1.73 m², dapagliflozin 10 mg daily can be initiated, though it will have reduced glucose-lowering efficacy 1, 2
• For patients with eGFR <25 mL/min/1.73 m², initiation of dapagliflozin is not recommended 1, 3
• Dapagliflozin should not be initiated in patients on dialysis due to lack of proven efficacy and safety data 4

Continuation Guidelines Based on eGFR

• If eGFR falls below 25 mL/min/1.73 m² during treatment, dapagliflozin 10 mg daily may be continued if tolerated for kidney and cardiovascular benefits until dialysis 1, 5
• If eGFR falls below 20 mL/min/1.73 m², dapagliflozin may still be continued if tolerated for kidney and cardiovascular benefits until dialysis 1
• Patients who experience an acute reduction in eGFR after starting dapagliflozin actually show a slower long-term eGFR decline compared to those without an initial drop 6

Evidence from Clinical Trials

• The DAPA-CKD trial demonstrated significant benefits of dapagliflozin in patients with eGFR between 25-75 mL/min/1.73 m² and albuminuria (UACR 200-5000 mg/g) 1
• Dapagliflozin reduced the risk of the composite outcome of sustained decline in eGFR of ≥50%, end-stage kidney disease, or renal or cardiovascular death by 39% (HR 0.61 [95% CI 0.51-0.72]) 1
• The DELIVER trial showed that dapagliflozin slowed the rate of eGFR decline compared with placebo in patients with heart failure, including those with eGFR <45 mL/min/1.73 m² 7
• A pooled analysis of DAPA-HF and DELIVER trials showed that patients who experienced deterioration of eGFR to <25 mL/min/1.73 m² still benefited from continuation of dapagliflozin without excess safety concerns 5

Important Considerations and Monitoring

• Glucose-lowering efficacy of dapagliflozin decreases substantially with declining renal function, making it ineffective for glycemic control in patients with eGFR <45 mL/min/1.73 m² 1, 2
• Despite reduced glucose-lowering effects, cardiovascular and kidney benefits are preserved at lower eGFR levels 1, 2
• Assess renal function prior to initiation and periodically thereafter 2
• Evaluate volume status before starting dapagliflozin and correct volume depletion if present 2
• Temporarily withhold dapagliflozin for at least 3 days prior to major surgery or procedures requiring prolonged fasting 2

Adverse Effects to Monitor

• Genital mycotic infections and urinary tract infections are common adverse effects that require monitoring 2, 8
• Volume depletion and euglycemic diabetic ketoacidosis are potential adverse effects that require vigilance 2
• Patients with diabetes and renal impairment using dapagliflozin may be more likely to experience hypotension and may be at higher risk for acute kidney injury secondary to volume depletion 3

By following these guidelines, clinicians can safely prescribe dapagliflozin to appropriate patients with chronic kidney disease while maximizing cardiovascular and renal benefits.