What class of medications is Farxiga (dapagliflozin)?

Farxiga (Dapagliflozin) Medication Classification

Farxiga (dapagliflozin) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor, a class of medications that works by blocking glucose reabsorption in the kidneys, thereby increasing urinary glucose excretion and reducing blood glucose levels.

Mechanism of Action

• Dapagliflozin selectively inhibits SGLT2, a transporter protein expressed in the proximal renal tubules that is responsible for the majority of glucose reabsorption from the tubular lumen 1
• By inhibiting SGLT2, dapagliflozin promotes urinary glucose excretion (glucosuria), which leads to reduced blood glucose levels 1, 2
• This mechanism is insulin-independent, making it complementary to other antidiabetic medications that work through different pathways 2
• Beyond glucose control, dapagliflozin also reduces sodium reabsorption and affects several physiological functions including:
  • Lowering pre- and afterload of the heart
  • Downregulation of sympathetic activity
  • Decreasing intraglomerular pressure through tubuloglomerular feedback 1

Clinical Benefits Beyond Glucose Control

SGLT2 inhibitors like dapagliflozin provide several important benefits:

1. Cardiovascular benefits:

   • Reduced risk of hospitalization for heart failure 3
   • Cardiovascular death reduction 3
   • Benefits in both heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) 3

2. Renal protection:

   • Slows progression of chronic kidney disease 3
   • Reduces risk of renal endpoints 3
   • Can be used with benefit down to an eGFR of 30 mL/min/1.73m² 3

3. Additional benefits:

   • Weight reduction of 1.5-3.5 kg 4
   • Lowering of systolic blood pressure by 3-5 mmHg 4
   • Low risk of hypoglycemia when used alone or with metformin 2

Distinguishing Features of SGLT2 Inhibitors

• SGLT2 inhibitors are unique among diabetes medications as they do not affect blood pressure, heart rate, or potassium levels, and require no dose adjustment or up-titration 3
• The most selective SGLT2 inhibitors are dapagliflozin, empagliflozin, and ertugliflozin 4
• Dapagliflozin typically reduces HbA1c by approximately 0.5-1.0% 4

Common Side Effects and Precautions

• Genital mycotic infections, particularly in women, are the most common adverse events 2
• Mild urinary tract infections may occur 5
• Risk of euglycemic ketoacidosis (rare in Type 2 diabetes) 3
• Not recommended in patients with moderate to severe renal impairment (eGFR <45 mL/min/1.73m²) for glycemic control, though it may still provide cardiovascular and renal benefits at lower eGFR levels 1

Clinical Positioning

According to current guidelines, SGLT2 inhibitors like dapagliflozin are recommended:

• As add-on therapy to metformin or other glucose-lowering agents 3
• For patients with established cardiovascular disease or multiple cardiovascular risk factors 3
• For patients with heart failure, particularly those with HFrEF 3
• For patients with chronic kidney disease to slow disease progression 3

In summary, Farxiga (dapagliflozin) belongs to the SGLT2 inhibitor class of medications, with a unique mechanism of action that provides benefits beyond glycemic control, including cardiovascular and renal protection.