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

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

Farxiga (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, particularly when metformin cannot be tolerated or when other glucose-lowering medications provide inadequate control. 1

Primary Indications in Type 2 Diabetes

Dapagliflozin is approved for use in type 2 diabetes in the following scenarios:

• Monotherapy: When diet and exercise alone are insufficient for glycemic control and the patient is unable to tolerate metformin
• Add-on therapy: In combination with other glucose-lowering agents including insulin, metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, or GLP-1 receptor agonists when these medications with diet and exercise do not provide adequate glycemic control 1, 2

Dosing in Type 2 Diabetes

• Adults: The recommended starting dose is 10 mg once daily
• Pediatric patients (10-17 years): Starting dose of 5 mg once daily, with potential up-titration to 10 mg if HbA1c remains ≥7% after 14 weeks 1
• Renal function considerations:
  • Not recommended for initiation if eGFR <25 mL/min/1.73 m²
  • Can be continued in patients with eGFR ≥25 mL/min/1.73 m² 3

Clinical Benefits in Type 2 Diabetes

Dapagliflozin provides several benefits in type 2 diabetes management:

1. Glycemic control:

   • Reduces HbA1c by approximately 0.5-0.7% compared to placebo 3
   • Decreases fasting plasma glucose and postprandial glucose levels 2, 4

2. Weight reduction:

   • Consistently associated with weight loss in clinical trials 2, 4
   • Weight reduction is maintained during long-term treatment (up to 2 years) 4

3. Low hypoglycemia risk:

   • Low intrinsic propensity to cause hypoglycemia when used as monotherapy or with metformin 5
   • Risk increases when combined with insulin or insulin secretagogues 4

4. Cardiovascular and renal benefits:

   • Reduces risk of hospitalization for heart failure in patients with type 2 diabetes with established cardiovascular disease or multiple cardiovascular risk factors 1
   • Provides renal protection with slower decline in kidney function 3

Special Populations

• Pediatric patients: Safety and efficacy established in patients aged 10 years and older with type 2 diabetes 1
• Elderly patients: No dosage adjustment recommended based on age, but higher incidence of hypotension-related adverse events in patients ≥65 years 1
• Renal impairment: Efficacy demonstrated in patients with moderate renal impairment (eGFR 45 to <60 mL/min/1.73 m²) 1

Safety Considerations

• Common adverse effects:

  • Genital mycotic infections (particularly in women)
  • Urinary tract infections
  • Volume depletion/hypotension
  • Euglycemic diabetic ketoacidosis (rare but serious) 3, 4

• Precautions:

  • Should be withheld for at least 3 days before major surgery or procedures requiring prolonged fasting
  • Resume when patient is clinically stable and has resumed oral intake 3
  • Not recommended during breastfeeding due to potential risk to developing kidneys 1

Mechanism of Action

Dapagliflozin works through a unique insulin-independent mechanism:

• Selectively inhibits sodium-glucose co-transporter-2 (SGLT2) in the renal proximal tubule
• Reduces renal glucose reabsorption, leading to increased urinary glucose excretion
• Lowers blood glucose levels independently of insulin secretion or action 2, 5

This distinctive mechanism makes dapagliflozin particularly valuable as an add-on therapy with other antidiabetic medications that work through different pathways.