What is the recommended use and dosage of Dapagliflozin (Forxiga) for patients with type 2 diabetes?

Dapagliflozin (Forxiga) for Type 2 Diabetes

For patients with type 2 diabetes, dapagliflozin is recommended at a starting dose of 5 mg once daily, which can be increased to 10 mg once daily for additional glycemic control. 1

Indications

• Dapagliflozin is 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
• It is also indicated to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors 2, 1
• Additional indications include reducing the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure, regardless of diabetes status 3, 1
• Dapagliflozin can reduce the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in adults with chronic kidney disease at risk of progression 1

Dosing Recommendations

• For glycemic control in type 2 diabetes:
  • Starting dose: 5 mg orally once daily 1
  • Dose can be increased to 10 mg once daily for additional glycemic control 1
• For cardiovascular and renal indications:
  • Fixed dose of 10 mg orally once daily 2, 3, 1
• Administration can be with or without food 1

Renal Function Considerations

• Prior to initiation, assess renal function and volume status 1
• For glycemic control:
  • Standard dosing for patients with eGFR ≥45 mL/min/1.73 m² 1
  • Not recommended for glycemic control in patients with eGFR <45 mL/min/1.73 m² as it is likely to be ineffective in this setting 1
• For cardiovascular and renal indications:
  • Standard dosing for patients with eGFR ≥25 mL/min/1.73 m² 1
  • Not recommended to initiate in patients with eGFR <25 mL/min/1.73 m² 1

Clinical Benefits

• Provides sustained, dose-dependent reduction in plasma glucose levels with HbA1c reductions ranging from 0.54-0.89% over 12-24 weeks 4
• Maintains efficacy over long-term treatment with HbA1c reductions of 0.58% at 52 weeks and 0.35% at 104 weeks compared to placebo 5
• Stabilizes insulin dosing in patients on high-dose insulin therapy, while placebo groups typically require insulin dose increases 6
• Produces modest weight loss of approximately 1-3 kg 4, 5, 6
• Reduces systolic blood pressure by 2-5 mmHg and diastolic blood pressure by 1.5-3 mmHg 4, 5

Safety Considerations

• Temporary interruption of dapagliflozin is recommended for at least 3 days before major surgery or procedures with prolonged fasting 2, 1
• Resume dapagliflozin when the patient is clinically stable and has resumed oral intake 1
• Low risk of hypoglycemia when used as monotherapy, but monitor patients when used with insulin or insulin secretagogues 2, 7
• Consider reducing insulin dose by approximately 20% when starting dapagliflozin to prevent hypoglycemia in patients on insulin therapy 2
• Monitor for diabetic ketoacidosis, a rare but serious adverse effect 2, 1
• Contraindicated in patients with history of serious hypersensitivity reaction to dapagliflozin 1

Common Adverse Effects

• Genital fungal infections (7.4-14.3% vs 3.0% with placebo) 6
• Urinary tract infections (8.4-13.8% vs 5.6% with placebo) 6
• Most infections occur in the first 24 weeks, are typically single episodes, and respond to routine management 6
• Volume depletion may occur, especially in elderly patients or those on diuretics 8

Special Populations

• Effective in older adults (≥65 years) with similar efficacy and safety profile as in younger patients 8
• Particularly beneficial for patients with established cardiovascular disease due to its cardiovascular risk reduction properties 2, 3
• Effective in patients with longer duration of diabetes (mean 13 years) and those requiring insulin therapy 8

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 3
• The DAPA-HF Trial demonstrated a 26% reduction in the composite of worsening heart failure or cardiovascular death in patients with heart failure with reduced ejection fraction, regardless of diabetes status 3
• Assess volume status before initiation and correct volume depletion if present 3
• Consider reducing diuretic dose if patient is at risk for volume depletion 3