What is the recommended use and dosage of Farxiga (dapagliflozin) for patients with type 2 diabetes and heart failure?

Farxiga (Dapagliflozin): Recommended Use and Dosing

Farxiga (dapagliflozin) 10 mg once daily is strongly recommended for all adults with symptomatic heart failure regardless of ejection fraction or diabetes status, and for patients with type 2 diabetes at cardiovascular risk, with a starting dose of 5 mg once daily for glycemic control that can be increased to 10 mg if needed. 1, 2

Primary Indications and Dosing

Heart Failure (All Ejection Fractions)

• Dose: 10 mg orally once daily for reducing cardiovascular death, heart failure hospitalization, and urgent heart failure visits in adults with symptomatic heart failure 2
• Dapagliflozin reduces the primary composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85) in patients with HFrEF (ejection fraction ≤40%) 1
• In heart failure with preserved or mildly reduced ejection fraction (>40%), dapagliflozin reduces worsening heart failure or cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) 1
• Benefits are consistent regardless of diabetes status, with similar efficacy in patients with normoglycemia, prediabetes, and type 2 diabetes 3

Type 2 Diabetes Mellitus

• Starting dose: 5 mg orally once daily in adults and pediatric patients aged 10 years and older 2
• Can increase to 10 mg once daily for additional glycemic control 2
• For patients with established cardiovascular disease or multiple risk factors, use 10 mg once daily to reduce heart failure hospitalization risk 2

Chronic Kidney Disease

• Dose: 10 mg orally once daily to reduce sustained eGFR decline, end-stage kidney disease, cardiovascular death, and heart failure hospitalization 2
• Dapagliflozin reduces the composite of ≥50% sustained eGFR decline, progression to ESKD, or cardiovascular/renal death by 39% (HR 0.61,95% CI 0.51-0.72) 1

Renal Function Considerations

For Glycemic Control in Type 2 Diabetes

• eGFR ≥45 mL/min/1.73 m²: Use standard dosing (5-10 mg daily) 2
• eGFR <45 mL/min/1.73 m²: NOT recommended for glycemic control—dapagliflozin is ineffective due to its mechanism of action 2

For Heart Failure and Chronic Kidney Disease Indications

• eGFR ≥25 mL/min/1.73 m²: Use 10 mg once daily 2
• eGFR <25 mL/min/1.73 m²: Do NOT initiate therapy 2
• If eGFR falls below 25 mL/min/1.73 m² during treatment: Continue dapagliflozin 10 mg daily to maintain renal and cardiovascular benefits 2
• Dapagliflozin can be used with caution when combined with high-dose loop diuretics due to enhanced natriuresis 1

Clinical Implementation Strategy

Timing of Initiation

• Initiate during heart failure hospitalization in stabilized patients, as deferring initiation results in high likelihood that eligible patients will never receive the medication within 1 year 1
• Dapagliflozin provides incremental benefit regardless of whether patients are already on optimal guideline-directed medical therapy (ACE inhibitor/ARB, beta-blocker, and mineralocorticoid receptor antagonist) 1

Pre-Treatment Assessment

• Assess renal function (eGFR) prior to initiation 2
• Assess volume status and correct volume depletion before starting therapy 2
• Continue existing guideline-directed medical therapy as dapagliflozin provides additive benefit 1

Surgical Considerations

• Withhold for at least 3 days prior to major surgery or procedures with prolonged fasting to reduce diabetic ketoacidosis risk 2
• Resume when patient is clinically stable and has resumed oral intake 2

Safety Profile and Monitoring

Common Adverse Events

• Genital infections occur more frequently with dapagliflozin than placebo but are generally manageable 1, 4
• Urinary tract infections are more common compared to placebo 4, 5
• Symptomatic hypotension is rare (0.3% vs 0.5% with placebo in DAPA-HF) 1

Critical Safety Concerns

• Diabetic ketoacidosis risk, including euglycemic ketoacidosis, particularly in type 1 diabetes (where dapagliflozin is NOT recommended) 2
• Monitor for ketoacidosis during illness, fasting, or surgical procedures 2
• Volume depletion risk, especially when combined with diuretics—monitor particularly in elderly patients, those with low baseline blood pressure, or renal impairment 1, 2

Contraindications

• History of serious hypersensitivity reaction (anaphylaxis, angioedema) to dapagliflozin 2
• Contraindicated in patients on dialysis 1

Mechanism of Cardiovascular Benefit

• Dapagliflozin inhibits proximal tubular sodium-glucose reabsorption, leading to natriuresis that enhances diuretic efficacy and triggers tubuloglomerular feedback, causing afferent arteriolar vasoconstriction that prevents glomerular hyperfiltration 1
• Shifts cardiac metabolism toward ketone utilization, which requires less oxygen than glucose or fatty acid metabolism, directly improving myocardial energetics 1
• Reduces cardiac fibrosis and adverse remodeling through mechanisms complementary to RAAS inhibitors and beta-blockers 1
• Benefits are independent of glucose-lowering effects, representing direct cardiovascular benefit 1, 6