What is the appropriate dapagliflozin dose for chronic kidney disease stage 3 (eGFR 30–59 mL/min/1.73 m²) and is dapagliflozin recommended for stage 4 (eGFR 15–29 mL/min/1.73 m²)?

Dapagliflozin Dosing in CKD Stage 3 and 4

Standard Dose Across All Indications

For both CKD stage 3 (eGFR 30–59 mL/min/1.73 m²) and stage 4 (eGFR 15–29 mL/min/1.73 m²), dapagliflozin 10 mg once daily is the evidence-based dose for cardiovascular and renal protection, with no dose adjustment required based on kidney function. 1

Initiation Thresholds by Indication

For Cardiovascular and Renal Protection

• Initiate dapagliflozin 10 mg once daily when eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection, regardless of diabetes status. 2, 3, 1

• In CKD stage 3a (eGFR 45–59 mL/min/1.73 m²) and stage 3b (eGFR 30–44 mL/min/1.73 m²), start dapagliflozin 10 mg daily without dose adjustment. 3, 1

• In CKD stage 4 (eGFR 15–29 mL/min/1.73 m²), dapagliflozin can be initiated at 10 mg daily if eGFR ≥25 mL/min/1.73 m²; do not initiate if eGFR is <25 mL/min/1.73 m². 2, 3, 1

• If eGFR falls below 25 mL/min/1.73 m² during treatment, continue dapagliflozin 10 mg daily until dialysis is required. 3, 1

For Glycemic Control

• For glycemic control in type 2 diabetes, start dapagliflozin 5 mg once daily if eGFR ≥45 mL/min/1.73 m², with the option to increase to 10 mg once daily if additional glucose lowering is needed. 1

• Do not initiate dapagliflozin for glycemic control if eGFR <45 mL/min/1.73 m², as glucose-lowering efficacy is markedly reduced due to its mechanism of action. 3, 1

Evidence Supporting Use in Advanced CKD

Renal Outcomes

• The DAPA-CKD trial enrolled patients with eGFR 25–75 mL/min/1.73 m² and demonstrated that dapagliflozin 10 mg daily reduced the composite kidney outcome (sustained eGFR decline ≥50%, end-stage kidney disease, or renal death) by 44% (HR 0.56,95% CI 0.45–0.68). 4, 3

• The primary composite outcome (sustained eGFR decline ≥50%, end-stage kidney disease, or cardiovascular/renal death) was reduced by 39% (HR 0.61,95% CI 0.51–0.72). 4, 3

• Dapagliflozin slowed the chronic eGFR decline by 0.95 mL/min/1.73 m² per year compared with placebo. 5

Cardiovascular Outcomes

• Cardiovascular death or hospitalization for heart failure was reduced by 29% (HR 0.71,95% CI 0.55–0.92). 4, 3

• All-cause mortality was reduced by 31% (HR 0.69,95% CI 0.53–0.88). 4, 3

Consistency Across CKD Severity

• Benefits were consistent across KDIGO risk categories, including patients with very high risk (eGFR 25–29 mL/min/1.73 m²), with no interaction between baseline kidney function and treatment effect. 6

• The efficacy and safety profile was similar in patients with and without type 2 diabetes. 4

Pre-Initiation Assessment

• Assess eGFR prior to initiation; dapagliflozin can be started if eGFR ≥25 mL/min/1.73 m². 1, 3

• Evaluate volume status and correct any depletion before starting dapagliflozin. 1, 3

• Consider reducing concurrent loop or thiazide diuretic doses in patients at high risk for volume depletion, particularly elderly patients. 3

Expected eGFR Changes and Monitoring

• An acute, reversible eGFR decline of 2–5 mL/min/1.73 m² typically occurs within the first 2–4 weeks; this hemodynamic change should not prompt discontinuation. 3, 7

• Patients who experienced an acute eGFR reduction >10% at 2 weeks had better long-term renal outcomes, with a slower chronic eGFR decline (-1.58 vs -2.44 mL/min/1.73 m² per year) compared with those without an initial dip. 7

• Re-measure eGFR 1–2 weeks after initiation to assess the expected transient decrease. 3

Medication Adjustments

• Continue ACE inhibitors or ARBs unchanged when dapagliflozin is started; the combination provides additive renal protection. 3

• If the patient is on metformin and eGFR is 30–44 mL/min/1.73 m², reduce metformin to a maximum of 1000 mg daily. 2

• If eGFR is <30 mL/min/1.73 m², discontinue metformin but continue dapagliflozin for cardiovascular and renal protection. 2

• When adding dapagliflozin to insulin or sulfonylurea therapy, reduce doses of those agents to mitigate hypoglycemia risk. 3

Safety Precautions and Patient Education

• Withhold dapagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea to prevent volume depletion and euglycemic diabetic ketoacidosis. 3

• Stop dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting. 3

• Counsel patients that genital mycotic infections occur in approximately 6% of treated individuals versus 1% with placebo; emphasize daily hygiene. 3

• Warn about euglycemic diabetic ketoacidosis and advise immediate medical evaluation for malaise, nausea, vomiting, or abdominal pain even when blood glucose is normal. 3

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin when eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist despite reduced glucose-lowering efficacy. 3

• Do not stop dapagliflozin because of the expected initial eGFR dip in the first 2–4 weeks; this change is hemodynamic and reversible. 3, 7

• Do not reduce the dose below 10 mg for cardiovascular or renal indications, even at lower eGFR levels; all outcome trials used the fixed 10 mg dose. 3

• Do not withhold dapagliflozin in CKD stage 4 patients with eGFR 25–29 mL/min/1.73 m²; this population was included in DAPA-CKD and demonstrated significant benefit. 4, 6