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

Dapagliflozin for Type 2 Diabetes: Dosage and Recommended Use

Dapagliflozin should be prescribed at 10 mg orally once daily for patients with type 2 diabetes mellitus, with a starting dose of 5 mg daily when used for glycemic control. 1, 2

Indications and Benefits

Dapagliflozin is indicated for multiple purposes in type 2 diabetes:

• Primary glycemic control indication: As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older 2
• Cardiovascular protection: To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus with either established cardiovascular disease or multiple cardiovascular risk factors 1, 2
• Heart failure management: To reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure 2
• Renal protection: 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 2

Dosing Algorithm

1. For glycemic control:

   • Start with 5 mg orally once daily
   • Can be increased to 10 mg daily for additional glycemic control 2

2. For cardiovascular and renal benefits:

   • Use 10 mg orally once daily 1, 2

3. Renal function considerations:

   • For glycemic control:
     • eGFR ≥45 mL/min/1.73m²: Standard dosing
     • eGFR <45 mL/min/1.73m²: Not recommended for glycemic control (likely ineffective) 2
   • For CV/renal benefits:
     • eGFR ≥25 mL/min/1.73m²: Standard dosing (10 mg daily)
     • eGFR <25 mL/min/1.73m²: Not recommended for initiation, but may continue if already on treatment 2

Monitoring Requirements

• Assess renal function prior to initiation and periodically thereafter
• Evaluate volume status before starting; correct volume depletion if present
• Monitor for signs of diabetic ketoacidosis, especially in patients with type 1 diabetes (where it's not recommended) 2
• Temporarily discontinue at least 3 days before major surgery or procedures requiring prolonged fasting 2

Contraindications

• History of serious hypersensitivity reaction to dapagliflozin
• Not recommended for type 1 diabetes mellitus due to increased risk of diabetic ketoacidosis 2
• Pregnancy or breastfeeding 1

Adverse Effects to Monitor

• Genital fungal infections (more common with dapagliflozin than placebo) 1, 3
• Urinary tract infections 1, 3
• Diabetic ketoacidosis (rare but serious) 2, 3
• Volume depletion, especially in elderly patients or those on diuretics 1

Clinical Pearls

• When initiating dapagliflozin in patients already on insulin or insulin secretagogues, consider reducing the dose of these agents by approximately 20% to minimize hypoglycemia risk 1
• Dapagliflozin provides additional benefits beyond glycemic control, including weight reduction (average 4.54 kg over 102 weeks) and reduction in waist circumference 4
• The cardiovascular benefits of dapagliflozin appear to be a class effect of SGLT2 inhibitors and are independent of glucose-lowering effects 1
• Dapagliflozin has shown a 26% reduction in the primary endpoint of worsening heart failure or CV death (HR: 0.74; 95% CI: 0.65 to 0.85) in the DAPA-HF study 1, 5

Common Pitfalls to Avoid

• Do not initiate in patients with volume depletion without correction
• Avoid use in patients with history of diabetic ketoacidosis
• Remember to temporarily interrupt treatment before major surgery
• Do not use for glycemic control in patients with eGFR <45 mL/min/1.73m², as it will likely be ineffective for this purpose (though it may still provide cardiorenal benefits at eGFR ≥25 mL/min/1.73m²) 2

Dapagliflozin represents an important treatment option for type 2 diabetes that goes beyond glycemic control to offer significant cardiovascular and renal protection, with a generally favorable safety profile when used appropriately.