What is the recommended dose of Dapagliflozin (Forxiga) for patients with Heart Failure with Reduced Ejection Fraction (HFrEF) and diabetes and Chronic Kidney Disease (CKD)?

Dapagliflozin Dosing in HFrEF with Diabetes and CKD

The recommended dose of dapagliflozin for patients with HFrEF, diabetes, and CKD is 10 mg orally once daily, provided the eGFR is ≥25 mL/min/1.73 m² 1, 2.

Dosing Algorithm Based on eGFR

For eGFR ≥25 mL/min/1.73 m²:

• Initiate dapagliflozin 10 mg once daily for cardiovascular and renal protection in patients with HFrEF and CKD 1, 2.
• This fixed dose applies regardless of diabetes status and is used for heart failure and CKD indications 1, 3.

For eGFR <25 mL/min/1.73 m²:

• Do not initiate dapagliflozin 1, 2.
• However, if already on treatment when eGFR falls below 25 mL/min/1.73 m², continue 10 mg daily until dialysis is required 1, 2.

For eGFR <45 mL/min/1.73 m²:

• Dapagliflozin should not be used for glycemic control as it is likely ineffective due to its mechanism of action 1, 2.
• However, the 10 mg dose remains appropriate for cardiovascular and renal protection at eGFR 25-44 mL/min/1.73 m² 1, 3.

Evidence Supporting This Dosing

The DAPA-CKD trial demonstrated that dapagliflozin 10 mg daily in patients with CKD (eGFR 25-75 mL/min/1.73 m²) reduced the primary composite outcome of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death by 39% (HR 0.61,95% CI 0.51-0.72) 4, 5. 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) 4, 6.

Critically, these benefits were consistent regardless of diabetes status 4, 7. In patients with diabetes, the primary outcome hazard ratio was 0.64 (95% CI 0.52-0.79), and in those without diabetes, it was 0.50 (95% CI 0.35-0.72), with no significant interaction (p=0.24) 4.

Similarly, in patients with HFrEF, dapagliflozin 10 mg daily reduced worsening heart failure or cardiovascular death by 27% in patients without diabetes (HR 0.73,95% CI 0.60-0.88) and by 25% in those with diabetes (HR 0.75,95% CI 0.63-0.90), with no interaction (p=0.80) 7.

Pre-Initiation Assessment

Before starting dapagliflozin:

• Assess renal function (eGFR and creatinine) 2, 3.
• Evaluate volume status and correct any volume depletion before initiation 2, 3.
• Check for contraindications, including history of serious hypersensitivity reactions to dapagliflozin 2.

Monitoring After Initiation

Within 1-2 weeks of starting:

• Recheck eGFR and creatinine 3.
• An initial eGFR dip of 3-5 mL/min/1.73 m² is expected and reversible; this does not require discontinuation 3.
• If eGFR decreases >30% from baseline and signs of hypovolemia are present, reduce diuretic doses first before adjusting dapagliflozin 3.

Ongoing monitoring:

• Assess for volume depletion, especially in elderly patients, those on diuretics, or with low baseline blood pressure 3.
• Monitor for genital mycotic infections and urinary tract infections, which occur more frequently with SGLT2 inhibitors 1, 3.
• Educate patients about euglycemic diabetic ketoacidosis (DKA), particularly those on insulin 1, 3.

Critical Safety Considerations

Withhold dapagliflozin:

• At least 3 days before major surgery or procedures with prolonged fasting to prevent postoperative ketoacidosis 3, 2.
• During acute illness with fever, vomiting, diarrhea, or reduced oral intake to prevent DKA and volume depletion 3.
• Resume only after recovery and normal oral intake is re-established 3.

Insulin management:

• In insulin-requiring patients, maintain at least low-dose insulin when holding dapagliflozin during illness, as complete insulin cessation increases DKA risk 3.

Common Pitfalls to Avoid

• Do not use dapagliflozin for glycemic control if eGFR <45 mL/min/1.73 m²—it will be ineffective for glucose lowering, though cardiovascular and renal benefits persist 1, 2.
• Do not discontinue dapagliflozin solely due to an initial eGFR dip of 3-5 mL/min/1.73 m² in the first 1-4 weeks, as this is expected and associated with better long-term renal outcomes 3.
• Do not initiate if eGFR <25 mL/min/1.73 m², but continue if already on treatment when eGFR falls below this threshold 1, 2.
• Do not overlook sick day management—patients must be counseled to stop dapagliflozin during acute illness 3.