What is the maximum recommended dose of dapagliflozin (Forxiga) for type 2 diabetes mellitus and heart failure?

Maximum Recommended Dose of Dapagliflozin

The maximum recommended dose of dapagliflozin is 10 mg once daily for all approved indications, including type 2 diabetes mellitus, heart failure, and chronic kidney disease. 1, 2, 3

Dosing by Indication

Type 2 Diabetes Mellitus

• Start at 5 mg once daily and may increase to 10 mg once daily if additional glycemic control is needed 3
• The 10 mg dose represents the maximum approved dose for glucose-lowering 1, 3
• No further dose escalation beyond 10 mg is recommended or approved 2, 3

Heart Failure (HFrEF or HFpEF)

• Fixed dose of 10 mg once daily regardless of diabetes status 1, 2, 3
• No dose titration is needed or recommended for cardiovascular benefit 3
• This dose reduced the composite of worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85) in the DAPA-HF trial 1, 4

Chronic Kidney Disease

• Fixed dose of 10 mg once daily for renal and cardiovascular protection 2, 3
• This dose reduced the primary composite renal endpoint by 39% (HR 0.61,95% CI 0.51-0.72) in the DAPA-CKD trial 2
• Benefits are consistent across eGFR levels down to 25 mL/min/1.73 m² 2, 3

Renal Function Considerations

The maximum dose remains 10 mg daily regardless of renal function, but initiation criteria vary by indication:

For Glycemic Control

• eGFR ≥45 mL/min/1.73 m²: Start at 5 mg, may increase to 10 mg daily 2, 3
• eGFR <45 mL/min/1.73 m²: Do not initiate for glycemic control (ineffective due to mechanism of action) 2, 3

For Cardiovascular/Renal Protection

• eGFR ≥25 mL/min/1.73 m²: Initiate at 10 mg daily 2, 3
• eGFR <25 mL/min/1.73 m²: Do not initiate, but may continue 10 mg daily if already on treatment until dialysis 2, 3

Clinical Evidence Supporting Maximum Dose

The 10 mg dose was used in all major cardiovascular and renal outcome trials:

• DAPA-HF trial: 10 mg daily in 4,744 patients with HFrEF (58% without diabetes) showed significant reduction in cardiovascular death or worsening heart failure 1, 4
• DAPA-CKD trial: 10 mg daily demonstrated 44% reduction in kidney-specific composite outcomes (HR 0.56,95% CI 0.45-0.68) 2
• DECLARE-TIMI 58: 10 mg daily reduced hospitalization for heart failure or cardiovascular death 1

Pharmacokinetic Rationale

• Dapagliflozin exhibits dose-proportional plasma concentrations with a half-life of 10-12 hours 5, 6
• The 10 mg dose provides near-maximal SGLT2 inhibition for 24 hours 6
• Urinary glucose excretion at steady state with 10 mg is 41.1 g/24 hours, representing near-maximal effect 5
• Higher doses (tested up to 500 mg in research) showed no additional clinical benefit and are not approved 6

Common Pitfalls to Avoid

• Do not exceed 10 mg daily thinking higher doses will provide additional cardiovascular or renal benefit—no evidence supports this 2, 3
• Do not reduce the dose to 5 mg for heart failure or CKD indications—the fixed 10 mg dose was studied in outcome trials 1, 3
• Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 2
• Do not initiate for any indication if eGFR <25 mL/min/1.73 m², though continuation at 10 mg is acceptable if already on treatment 2, 3