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
• Dose: 10 mg once daily to reduce hospitalization for heart failure in patients with established cardiovascular disease or multiple cardiovascular risk factors 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 in adults with chronic kidney disease at risk of progression 2

Renal Dosing Considerations

For Glycemic Control

• Use standard dosing (5-10 mg daily) when eGFR ≥45 mL/min/1.73 m² 2
• Not recommended for glycemic control when eGFR <45 mL/min/1.73 m² as it is likely ineffective due to mechanism of action 2

For Heart Failure and Kidney Disease Indications

• Use standard 10 mg daily dosing when eGFR ≥25 mL/min/1.73 m² 2
• Do not initiate if eGFR <25 mL/min/1.73 m² 2
• If eGFR falls below 25 mL/min/1.73 m² during treatment, patients may continue 10 mg daily to reduce eGFR decline, end-stage kidney disease, cardiovascular death, and heart failure hospitalization 2
• Dapagliflozin provides renal benefits even in patients with eGFR as low as 25 mL/min/1.73 m², reducing the composite of ≥50% sustained eGFR decline, progression to end-stage kidney disease, or cardiovascular/renal death by 39% (HR 0.61,95% CI 0.51-0.72) 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
• Continue all existing guideline-directed medical therapy (ACE inhibitors, ARBs, ARNIs, beta-blockers, mineralocorticoid receptor antagonists) as dapagliflozin provides additive benefit 1

Pre-Treatment Assessment

• Assess renal function (eGFR) prior to initiation and monitor as clinically indicated 2
• Assess volume status and correct volume depletion before starting dapagliflozin 2

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

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, 4

Safety Profile and Monitoring

Common Adverse Events

• Genital infections occur more frequently with dapagliflozin than placebo 5, 6
• Urinary tract infections are more common but generally manageable 6
• Low risk of hypoglycemia when used alone or with metformin 5, 6

Critical Safety Considerations

• Monitor for diabetic ketoacidosis, including euglycemic ketoacidosis, particularly during illness, fasting, or in susceptible patients 2
• Symptomatic hypotension is rare (0.3% vs 0.5% with placebo in DAPA-HF), with minimal blood pressure effects 1
• Use with caution when combined with high-dose loop diuretics due to enhanced natriuresis 1
• Monitor for volume depletion, especially in elderly patients, those with low baseline blood pressure, or patients on diuretics 2

Contraindications

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

Comparative Effectiveness

• Dapagliflozin and empagliflozin are both effective across the ejection fraction spectrum (HFrEF and HFpEF) for heart failure benefits 4
• All SGLT2 inhibitors provide similar glycemic control, typically reducing HbA1c by approximately 0.7-1.0% when added to metformin 4
• Dapagliflozin provides robust renal protection, reducing composite renal outcomes by 44% (HR 0.56,95% CI 0.45-0.68) 1