What is the maximum recommended daily dose of dapagliflozin in adults, and how should dosing be adjusted for patients with moderate to severe renal impairment (eGFR <45 mL/min/1.73 m² for diabetes or <30 mL/min/1.73 m² for heart failure/CKD)?

Maximum Daily Dose of Dapagliflozin

The maximum recommended daily dose of dapagliflozin is 10 mg once daily for all approved indications, including type 2 diabetes, heart failure, and chronic kidney disease—no higher dose provides additional cardiovascular or renal benefit, and dose titration is not required. 1, 2

Standard Dosing Across All Indications

• For glycemic control in type 2 diabetes: Start with 5 mg once daily in patients with eGFR ≥45 mL/min/1.73 m², and may increase to 10 mg once daily if additional glucose lowering is needed. 1

• For cardiovascular and renal protection (heart failure or chronic kidney disease): Use a fixed dose of 10 mg once daily—this is the evidence-based dose from all major outcome trials (DAPA-CKD, DAPA-HF, DELIVER), and no titration is required. 1, 2, 3, 4

• The 10 mg dose is the ceiling dose—no formulation or dosing regimen above 10 mg daily exists or is approved for dapagliflozin. 1, 2, 5

Renal Function-Based Dosing Adjustments

For Glycemic Control (Type 2 Diabetes)

• eGFR ≥45 mL/min/1.73 m²: Initiate at 5 mg once daily; may increase to 10 mg once daily if needed for glycemic control. 1, 2

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

For Cardiovascular and Renal Protection (Heart Failure or CKD)

• eGFR 25 to <45 mL/min/1.73 m²: Use 10 mg once daily for cardiovascular and renal protection—glucose-lowering efficacy is minimal, but mortality and kidney-failure benefits are fully preserved. 1, 2, 3, 4

• eGFR <25 mL/min/1.73 m²: Initiation is not recommended; however, if a patient is already on dapagliflozin 10 mg daily when eGFR falls below 25 mL/min/1.73 m², the drug may be continued until dialysis is required. 1, 2, 5

• Dialysis: Dapagliflozin is contraindicated in patients on dialysis. 1, 5

Evidence Supporting the 10 mg Maximum Dose

• DAPA-CKD trial (4,304 patients with CKD and albuminuria): Dapagliflozin 10 mg once daily reduced the primary composite outcome (≥50% sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death) by 39% (HR 0.61,95% CI 0.51–0.72). 2, 3, 4

• Kidney-specific outcomes: The same 10 mg dose reduced the composite of sustained eGFR decline, end-stage renal disease, or renal death by 44% (HR 0.56,95% CI 0.45–0.68). 2, 3

• Cardiovascular outcomes: Dapagliflozin 10 mg daily reduced cardiovascular death or heart failure hospitalization by 29% (HR 0.71,95% CI 0.55–0.92) and all-cause mortality by 31% (HR 0.69,95% CI 0.53–0.88). 2, 3, 4

• Consistency across diabetes status: Benefits were identical in patients with type 2 diabetes (67.5% of trial participants) and those without diabetes (32.5%), confirming that 10 mg is the optimal dose regardless of glycemic needs. 2, 4

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 of dapagliflozin initiation—this hemodynamic dip reflects reduced intraglomerular pressure and should not prompt discontinuation. 2, 6

• Patients who experience an acute eGFR reduction >10% at 2 weeks have better long-term renal outcomes (slower eGFR decline of -1.58 vs -2.44 mL/min/1.73 m²/year) compared to those without an initial dip, demonstrating that the early decline is protective, not harmful. 6

• Re-measure eGFR 1–2 weeks after initiation, then every 3–6 months if eGFR is 25–59 mL/min/1.73 m², or annually if eGFR ≥60 mL/min/1.73 m². 2

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin when eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal benefits persist even when glucose-lowering efficacy is lost. 1, 2

• Do not stop dapagliflozin in response to the expected early eGFR dip—this change is hemodynamic and reversible, not indicative of kidney injury. 2, 6

• 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, and no evidence supports dose reduction. 1, 2, 3

• Do not attempt to titrate above 10 mg—no higher dose exists, and the 10 mg dose delivers the full mortality-reducing and kidney-protective effect observed in clinical trials. 1, 2

Safety Precautions

• Temporarily withhold dapagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea, and stop at least 3 days before major surgery or procedures requiring prolonged fasting to prevent euglycemic diabetic ketoacidosis. 2

• Genital mycotic infections occur in approximately 6% of dapagliflozin users versus 1% with placebo—counsel patients on daily hygiene measures. 2

• Assess volume status before initiation and consider reducing concurrent diuretic doses in elderly patients or those at high risk for volume depletion. 2

• If dapagliflozin is combined with insulin or sulfonylureas, reduce the doses of those agents by ~20% to mitigate hypoglycemia risk, and monitor glucose closely for the first 2–4 weeks. 2