What are the indications and usage of Farxiga (dapagliflozin) in patients with type 2 diabetes and heart failure?

Farxiga (Dapagliflozin): Indications and Usage

Farxiga (dapagliflozin) 10 mg daily is indicated for multiple cardiovascular and renal conditions beyond glycemic control, including reducing hospitalization for heart failure in patients with type 2 diabetes and established cardiovascular disease or multiple risk factors, treating heart failure with reduced ejection fraction regardless of diabetes status, and reducing progression of chronic kidney disease. 1

FDA-Approved Indications

Dapagliflozin has four distinct FDA-approved indications 1:

• Chronic Kidney Disease: Reduces sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression 1

• Heart Failure (Any Diabetes Status): Reduces cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure, regardless of whether they have diabetes 1, 2

• Type 2 Diabetes with Cardiovascular Risk: Reduces hospitalization for heart failure in adults with type 2 diabetes and either established cardiovascular disease or multiple cardiovascular risk factors 1, 3

• Glycemic Control: Adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes 1

Dosing

The standard dose is 10 mg orally once daily for all cardiovascular and renal indications. 4, 3, 2

Key Limitations of Use

Critical restrictions apply to specific populations 1:

• Not recommended for glycemic control in type 1 diabetes due to increased ketoacidosis risk 1

• Not recommended for glycemic control when eGFR <45 mL/min/1.73 m² as it is likely ineffective based on mechanism of action 1, 4

• Contraindicated when eGFR <30 mL/min/1.73 m² 4

• Not recommended for chronic kidney disease in patients with polycystic kidney disease or those requiring/recently receiving immunosuppressive therapy for kidney disease 1

Cardiovascular Benefits in Type 2 Diabetes

Heart Failure Reduction

Dapagliflozin demonstrates robust heart failure benefits in patients with type 2 diabetes 5:

• DECLARE-TIMI 58 trial (17,160 patients with type 2 diabetes) showed a 27% reduction in hospitalization for heart failure (HR 0.73; 95% CI 0.61-0.88) 5, 2

• The composite endpoint of cardiovascular death or hospitalization for heart failure was reduced by 17% (HR 0.83; 95% CI 0.73-0.95) 5

• Benefits were consistent regardless of baseline use of ACE inhibitors/ARBs, beta-blockers, diuretics, or mineralocorticoid receptor antagonists 6

Heart Failure with Reduced Ejection Fraction

DAPA-HF trial demonstrated a 26% reduction in the composite of worsening heart failure or cardiovascular death (HR 0.74; 95% CI 0.65-0.85) in patients with heart failure and reduced ejection fraction, regardless of diabetes status. 4, 2

Additional DAPA-HF findings include 2, 7:

• 30% relative risk reduction in hospitalizations for heart failure 8
• 57% relative risk reduction in urgent heart failure visits 8
• 18% relative risk reduction in cardiovascular death 8

Renal Protection

Dapagliflozin provides significant renal benefits 5:

• 47% reduction in composite renal events (HR 0.53; 95% CI 0.43-0.66) in DECLARE-TIMI 58 5

• In patients with chronic kidney disease, 39% reduction in the composite of sustained eGFR decline ≥50%, end-stage renal disease, or renal/cardiovascular death (HR 0.61; 95% CI 0.51-0.72) 5

Safety Considerations and Monitoring

Perioperative Management

Discontinue dapagliflozin at least 3 days before major surgery or procedures with prolonged fasting to prevent postoperative ketoacidosis. 4, 3, 2

Resume only when the patient is clinically stable and has resumed oral intake 3

Volume Status

Assess volume status before initiation and correct volume depletion if present 2. Consider reducing diuretic dose if the patient is at risk for volume depletion 2. Dapagliflozin may contribute to intravascular volume contraction 4.

Diabetic Ketoacidosis

Monitor for diabetic ketoacidosis, a rare but serious adverse effect 3, 2. The risk is particularly elevated in type 1 diabetes, which is why dapagliflozin is not recommended for this population 1.

Insulin Dose Adjustment

When starting dapagliflozin in patients on insulin, consider reducing total daily insulin dose by approximately 20% to prevent hypoglycemia. 4, 3

Similarly, if HbA1c is well-controlled at baseline or there is a history of frequent hypoglycemic events, wean or stop sulfonylurea or glinide therapy 4.

Common Adverse Effects

Monitor for 4, 2:

• Genital fungal infections
• Urinary tract infections
• Euglycemic diabetic ketoacidosis

Special Cautions

Use with caution in patients with 4:

• Prior amputation
• Severe peripheral neuropathy
• Severe peripheral vascular disease
• Active diabetic foot ulcers or soft tissue infections

Clinical Practice Algorithm

For patients with type 2 diabetes:

1. If established cardiovascular disease or multiple cardiovascular risk factors present → Initiate dapagliflozin 10 mg daily to reduce hospitalization for heart failure 3, 1

2. If heart failure with reduced ejection fraction present → Initiate dapagliflozin 10 mg daily regardless of diabetes status 1, 2

3. If chronic kidney disease at risk of progression → Initiate dapagliflozin 10 mg daily 1

4. Check eGFR before initiation:

   • eGFR ≥45 mL/min/1.73 m² → Proceed with dapagliflozin for all indications 4
   • eGFR 30-44 mL/min/1.73 m² → Use for cardiovascular/renal indications but not for glycemic control 1
   • eGFR <30 mL/min/1.73 m² → Contraindicated 4, 1

5. Adjust concomitant medications:

   • Reduce insulin by ~20% 4, 3
   • Consider stopping/reducing sulfonylurea if HbA1c well-controlled 4
   • Consider reducing diuretic dose if volume depletion risk 2

6. Hold 3 days before major surgery 4, 3, 2