How is the dose of dapagliflozin (Forxiga) adjusted based on estimated Glomerular Filtration Rate (eGFR) in patients with type 2 diabetes?

Dapagliflozin Dosing Based on eGFR

Dapagliflozin dosing depends on the indication: for glycemic control in type 2 diabetes, do not initiate if eGFR <45 mL/min/1.73 m²; for cardiovascular and renal protection (heart failure or chronic kidney disease), use 10 mg daily if eGFR ≥25 mL/min/1.73 m². 1, 2, 3

Dosing Algorithm by Indication and eGFR

For Glycemic Control in Type 2 Diabetes

• eGFR ≥45 mL/min/1.73 m²: Start with 5 mg once daily, may increase to 10 mg once daily if additional glycemic control is needed 1, 3

• eGFR <45 mL/min/1.73 m²: Do not initiate dapagliflozin for glycemic control, as glucose-lowering efficacy is significantly reduced due to the drug's mechanism of action (inhibition of renal SGLT2) 1, 2, 3

• eGFR <30 mL/min/1.73 m² without established cardiovascular disease: Not recommended for initiation 3

For Cardiovascular and Renal Protection (Heart Failure or CKD)

• eGFR ≥25 mL/min/1.73 m²: Use fixed dose of 10 mg once daily regardless of diabetes status 1, 2, 3

• eGFR <25 mL/min/1.73 m²: Initiation is not recommended; however, if already on treatment, may continue 10 mg daily in patients with heart failure or CKD until dialysis is initiated 1, 2, 3

• On dialysis: Contraindicated 1, 3

Critical Monitoring After Initiation

An acute eGFR decline of 2-5 mL/min/1.73 m² within the first 1-4 weeks is expected and reversible. 2, 4, 5 This initial dip does not predict worse outcomes; in fact, patients experiencing an acute eGFR reduction >10% at 2 weeks had better long-term renal outcomes with slower eGFR decline (-1.58 vs -2.44 mL/min/1.73 m²/year) compared to those without an initial dip 5.

• Check eGFR and creatinine within 1-2 weeks after initiation 2
• Evaluate volume status before starting and monitor closely for intravascular volume contraction 2, 3
• If eGFR decreases >30% from baseline AND there are signs of hypovolemia, reduce diuretic doses first before considering dapagliflozin adjustment 2
• eGFR typically returns to near baseline by week 24 and remains stable long-term 6, 4

Evidence Supporting Renal and Cardiovascular Benefits

The DAPA-CKD trial demonstrated that dapagliflozin 10 mg daily in patients with CKD (eGFR 25-75 mL/min/1.73 m²) and albuminuria (UACR 200-5000 mg/g) reduced the primary composite outcome (sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death) by 39% (HR 0.61 [95% CI 0.51-0.72]) 1. The renal composite outcome was reduced by 44% (HR 0.56 [95% CI 0.45-0.68]), and cardiovascular death or heart failure hospitalization was reduced by 29% (HR 0.71 [95% CI 0.55-0.92]) 1, 2. These benefits were consistent in patients with and without type 2 diabetes 1.

Dapagliflozin slowed the chronic eGFR decline by 2.26 mL/min/1.73 m² per year in patients with type 2 diabetes and 1.29 mL/min/1.73 m² per year in those without diabetes compared to placebo 7. The protective effect was more pronounced in patients with higher baseline HbA1c and albuminuria 7.

Common Pitfalls and Safety Considerations

Withhold dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 2, 3

During acute illness (fever, vomiting, diarrhea, reduced oral intake), temporarily discontinue dapagliflozin to prevent diabetic ketoacidosis and volume depletion. 2 Monitor for euglycemic DKA even with normal blood glucose levels 2. Resume only after recovery and normal oral intake is re-established 2.

• Use caution in elderly patients (≥65 years), those on diuretics, or with low systolic blood pressure due to increased risk of hypotension and volume depletion 2, 3
• Genital mycotic infections occur more frequently with dapagliflozin; educate patients on hygiene measures and symptom recognition 2, 8
• In patients with eGFR 30-60 mL/min/1.73 m², there was an increased risk of bone fractures in one trial (13 patients vs 0 on placebo) 3
• Maintain at least low-dose insulin in insulin-requiring patients when holding dapagliflozin during illness, as complete insulin cessation increases DKA risk 2

Special Populations

Patients ≥65 years: No dose adjustment needed, though higher rates of hypotension were observed in this age group when used for glycemic control 3. In the DAPA-CKD, DAPA-HF, and DELIVER trials, safety and efficacy were similar across age groups 3.

Hepatic impairment: No dose adjustment required for mild, moderate, or severe hepatic impairment, though benefit-risk should be individually assessed in severe hepatic impairment 3.