What is the recommended use and dosage of Dapagliflozin (SGLT2 inhibitor) for patients with type 2 diabetes or heart failure?

Dapagliflozin: Recommended Use and Dosage for Type 2 Diabetes and Heart Failure

Dapagliflozin should be administered at a dose of 10 mg orally once daily for patients with type 2 diabetes and/or heart failure, regardless of diabetes status, to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits. 1, 2, 3

Indications

Type 2 Diabetes

• Recommended as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus 3
• For patients with type 2 diabetes starting for glycemic control, the initial dose is 5 mg once daily, which can be increased to 10 mg once daily for additional glycemic control 3
• Reduces the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors 1, 2

Heart Failure

• Indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), regardless of diabetes status 2, 3
• The DAPA-HF trial demonstrated a 26% reduction in the composite of worsening heart failure or cardiovascular death in patients with HFrEF (HR 0.74; 95% CI 0.65-0.85) 1, 4
• The DELIVER trial showed an 18% reduction in the composite of worsening heart failure or cardiovascular death in patients with HFpEF 2

Chronic Kidney Disease

• Indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression 3

Dosing Considerations

Renal Function

• For glycemic control: Not recommended in patients with eGFR <45 mL/min/1.73 m² 1, 3
• For heart failure and chronic kidney disease indications: Can be used in patients with eGFR ≥25 mL/min/1.73 m² 3
• If eGFR falls below 25 mL/min/1.73 m² while on treatment, dapagliflozin may be continued at 10 mg daily to reduce the risk of eGFR decline, ESKD, CV death, and heart failure hospitalization 3

Perioperative Management

• Withhold dapagliflozin for at least 3 days before major surgery or procedures associated with prolonged fasting 1, 2, 3
• Resume when the patient is clinically stable and has resumed oral intake 3

Clinical Benefits

Cardiovascular Outcomes

• In patients with heart failure, dapagliflozin reduces:
  • Risk of worsening heart failure by 30% 4, 5
  • Risk of urgent heart failure visits by 57% 5
  • Risk of cardiovascular death by 18% 4, 5
• Benefits are consistent regardless of diabetes status 1, 4
• A meta-analysis of multiple SGLT2 inhibitor trials demonstrated reduced risk for the composite of cardiovascular death or hospitalization for heart failure across a wide range of heart failure patients 1

Renal Outcomes

• Reduces the risk of renal composite outcomes including sustained decline in eGFR, end-stage kidney disease, and renal death 1, 3

Safety Considerations

Common Adverse Effects

• Genital fungal infections 1, 2
• Urinary tract infections 1, 2
• Euglycemic diabetic ketoacidosis (rare but serious) 1, 2, 3

Special Precautions

• Assess volume status before initiation and correct volume depletion if present 2, 3
• Consider reducing diuretic dose in patients at risk for volume depletion 2
• Monitor for signs and symptoms of diabetic ketoacidosis, especially in patients with type 1 diabetes (dapagliflozin is not recommended for type 1 diabetes) 2, 3
• Contraindicated in patients with history of serious hypersensitivity reactions to dapagliflozin 3

Clinical Algorithm for Patient Selection

1. For patients with type 2 diabetes:

   • Start with 5 mg once daily for glycemic control 3
   • Increase to 10 mg once daily if additional glycemic control is needed 3
   • Use 10 mg once daily if the patient has established cardiovascular disease or multiple risk factors 1, 2

2. For patients with heart failure (with or without diabetes):

   • Use 10 mg once daily regardless of ejection fraction 2, 3, 4
   • Benefits observed in both HFrEF and HFpEF populations 1

3. For patients with chronic kidney disease:

   • Use 10 mg once daily if eGFR ≥25 mL/min/1.73 m² 3
   • Continue treatment even if eGFR falls below 25 mL/min/1.73 m² while on treatment 3

4. Contraindications and cautions:

   • Do not use for glycemic control if eGFR <45 mL/min/1.73 m² 1, 3
   • Assess volume status and correct depletion before starting 3
   • Temporarily discontinue 3 days before major surgery 1, 2, 3

Dapagliflozin's cardiovascular and renal benefits appear to be independent of its glucose-lowering effects, making it a valuable option for reducing morbidity and mortality in patients with type 2 diabetes and/or heart failure 2, 6, 4.