What is the recommended use of Dapagliflozin?

Recommended Use of Dapagliflozin

Dapagliflozin is recommended for multiple indications including glycemic control in type 2 diabetes, cardiovascular risk reduction, heart failure management, and chronic kidney disease progression prevention, with a standard dose of 10 mg once daily for most indications. 1

Approved Indications

• Glycemic Control: Indicated 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 1

  • Starting dose: 5 mg once daily
  • Can be increased to 10 mg once daily for additional glycemic control 1

• Cardiovascular Risk Reduction: Indicated to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors 1

  • Dose: 10 mg once daily 1

• Heart Failure Management: Indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure (with both reduced and preserved ejection fraction) 1

  • Dose: 10 mg once daily 1
  • Benefit observed regardless of diabetes status 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 1

  • Dose: 10 mg once daily 1

Dosage Adjustments Based on Renal Function

• For Glycemic Control:

  • eGFR ≥45 mL/min/1.73 m²: No dose adjustment needed 1
  • eGFR <45 mL/min/1.73 m²: Not recommended for glycemic control (likely ineffective) 1

• For Other Indications (heart failure, cardiovascular risk reduction, CKD):

  • eGFR ≥25 mL/min/1.73 m²: No dose adjustment needed 1
  • eGFR <25 mL/min/1.73 m²: Not recommended for initiation 1
  • If eGFR falls below 25 mL/min/1.73 m² during treatment, may continue 10 mg daily to reduce risk of eGFR decline, ESKD, CV death, and heart failure hospitalization 1

Clinical Evidence Supporting Recommendations

• DAPA-HF Trial: Demonstrated 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 with reduced ejection fraction, regardless of diabetes status 2, 3

• DELIVER Trial: Showed 18% reduction in the composite of worsening heart failure or cardiovascular death (HR 0.82; 95% CI 0.73-0.92) in patients with heart failure with preserved ejection fraction 2

• DECLARE-TIMI 58: Demonstrated cardiovascular safety and 27% reduction in hospitalization for heart failure in patients with type 2 diabetes with established cardiovascular disease or multiple risk factors 2

Important Safety Considerations

• Contraindications:

  • History of serious hypersensitivity reaction to dapagliflozin 1
  • Pregnancy or breastfeeding 2
  • eGFR <30 mL/min/1.73 m² (for glycemic control) 2

• Precautions:

  • Discontinue at least 3 days before planned surgery to prevent postoperative ketoacidosis 2, 1
  • Monitor for diabetic ketoacidosis, especially in patients with type 1 diabetes (not indicated) 1
  • Assess volume status before initiation and correct volume depletion if present 1
  • Consider reducing diuretic dose if patient is at risk for volume depletion 2

• Common Adverse Effects:

  • Genital fungal infections 2
  • Urinary tract infections 2
  • Euglycemic diabetic ketoacidosis (rare) 2

Clinical Pearls

• Dapagliflozin's cardiovascular and renal benefits appear to be independent of its glucose-lowering effects, as benefits are seen in patients with and without diabetes 2

• For patients with heart failure, dapagliflozin should be considered regardless of diabetes status, as it improves symptoms, physical limitations, and quality of life 2

• When used for cardiovascular or renal protection, the 10 mg dose should be used from the start without titration 2

• If HbA1c is well-controlled at baseline or patient has history of hypoglycemic events, consider reducing insulin dose by approximately 20% when starting therapy 2

• Dapagliflozin is not recommended for use in type 1 diabetes due to increased risk of diabetic ketoacidosis 1