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

Indications and Usage of Farxiga (Dapagliflozin) in Type 2 Diabetes and Heart Failure

Farxiga (dapagliflozin) is strongly indicated for patients with type 2 diabetes and heart failure to reduce the risk of worsening heart failure, cardiovascular death, and improve symptoms and quality of life, regardless of ejection fraction status. 1

Primary Indications

• Dapagliflozin is FDA-approved for improving glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise 2
• Dapagliflozin is indicated to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors 1, 2
• Dapagliflozin is approved to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure with reduced ejection fraction (HFrEF) 1, 2, 3
• Dapagliflozin is indicated for heart failure with preserved ejection fraction (HFpEF) based on the DELIVER trial results 1

Clinical Evidence for Heart Failure Indications

Heart Failure with Reduced Ejection Fraction (HFrEF)

• In the DAPA-HF trial, dapagliflozin reduced the composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74 [95% CI 0.65–0.85]) in patients with NYHA class II-IV heart failure and ejection fraction ≤40% 1
• Dapagliflozin reduced the risk of first worsening heart failure event by 30% (HR 0.70 [95% CI 0.59–0.83]) and cardiovascular death by 18% (HR 0.82 [95% CI 0.69–0.98]) compared to placebo 1
• Benefits were consistent regardless of diabetes status - 45% of participants had type 2 diabetes, but efficacy was similar in those with and without diabetes 1, 3

Heart Failure with Preserved Ejection Fraction (HFpEF)

• In the DELIVER trial, dapagliflozin reduced the composite of worsening heart failure (hospitalization or urgent visit) or cardiovascular death by 18% (HR 0.82 [95% CI 0.73–0.92]) in patients with heart failure and ejection fraction >40% 1
• Approximately 44% of participants had type 2 diabetes, and results were consistent regardless of diabetes status 1

Dosing and Administration

• The recommended dose is 10 mg orally once daily 2, 4
• No dose adjustment is needed based on diabetes status 1
• Dose modifications are required for renal impairment:
  • For glycemic control, dapagliflozin is not recommended when eGFR <45 mL/min/1.73 m² 1, 2
  • For heart failure indication, dapagliflozin can be used at lower eGFR levels but is contraindicated when eGFR <30 mL/min/1.73 m² 2

Safety Considerations

• Common adverse effects include:

  • Genital mycotic infections (monitor and treat appropriately) 2, 4
  • Urinary tract infections (evaluate and treat promptly) 2, 4
  • Volume depletion (monitor for signs of hypotension, especially in elderly patients or those on diuretics) 2

• Serious but rare adverse effects:

  • Diabetic ketoacidosis (including euglycemic ketoacidosis) - monitor especially during illness or fasting 2
  • Necrotizing fasciitis of the perineum (Fournier's gangrene) - requires urgent intervention if suspected 2
  • Hypoglycemia risk when used with insulin or insulin secretagogues - may require dose reduction of these agents 2

Clinical Implementation Algorithm

1. Patient Selection:

   • Identify patients with type 2 diabetes and established heart failure (either HFrEF or HFpEF) 1
   • Consider for patients with type 2 diabetes at high risk for heart failure even without established heart failure 1
   • Consider for patients with heart failure regardless of diabetes status 1

2. Pre-initiation Assessment:

   • Check renal function (eGFR) 2
   • Assess volume status and risk of volume depletion 2
   • Review concomitant medications, especially diuretics and other antihyperglycemics 2

3. Initiation and Monitoring:

   • Start with 10 mg once daily 2, 4
   • Monitor for genital mycotic infections and urinary tract infections 2
   • If patient is on insulin or insulin secretagogues, consider reducing their dose to prevent hypoglycemia 2
   • Educate patients about signs of ketoacidosis, genital infections, and volume depletion 2

4. Follow-up:

   • Assess for improvement in heart failure symptoms 1
   • Monitor renal function periodically 2
   • Continue therapy long-term as benefits on cardiovascular outcomes have been demonstrated in trials with follow-up of 18+ months 1

Important Clinical Pearls

• Dapagliflozin provides cardiovascular benefits independent of its glucose-lowering effects, as evidenced by similar efficacy in patients with and without diabetes 1, 3
• Consider temporarily discontinuing dapagliflozin at least 3 days before planned surgery to prevent postoperative ketoacidosis 1, 2
• Benefits appear to be a class effect of SGLT2 inhibitors, with similar results seen with empagliflozin and canagliflozin in their respective trials 1, 5
• The mechanism of cardiovascular benefit extends beyond glycemic control and likely involves hemodynamic effects, improved cardiac metabolism, and reduced cardiac fibrosis 4, 6