What type of medication is Farxiga (dapagliflozin)?

Farxiga (Dapagliflozin): A Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor

Farxiga (dapagliflozin) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that works by blocking glucose reabsorption in the kidneys, promoting urinary glucose excretion, and reducing blood glucose levels. 1, 2

Mechanism of Action

Dapagliflozin functions through:

• Primary mechanism: Inhibition of SGLT2 in the proximal renal tubules, reducing reabsorption of filtered glucose and promoting urinary glucose excretion 1
• Secondary effects: Reduces sodium reabsorption, increases sodium delivery to distal tubules, which:
  • Lowers pre- and afterload of the heart
  • Downregulates sympathetic activity
  • Decreases intraglomerular pressure through tubuloglomerular feedback 1

FDA-Approved Indications

Farxiga has expanded beyond its original use for diabetes and is now approved for:

1. Type 2 diabetes mellitus: As monotherapy or add-on to other antidiabetic medications 1, 3
2. Chronic kidney disease: To reduce risk of kidney function decline, kidney failure, and cardiovascular death 1, 4
3. Heart failure: To reduce risk of cardiovascular death and hospitalization in both:
   • Heart failure with reduced ejection fraction (HFrEF) 1, 5
   • Heart failure with preserved ejection fraction (HFpEF) 6

Clinical Benefits

Dapagliflozin has demonstrated significant benefits in multiple large clinical trials:

• Diabetes management: Effective glycemic control without risk of hypoglycemia when used as monotherapy 2, 3
• Cardiovascular protection: In the DECLARE-TIMI 58 trial, dapagliflozin reduced the composite of cardiovascular death or heart failure hospitalization by 17% 6
• Heart failure benefits: In DAPA-HF trial, reduced risk of worsening heart failure or cardiovascular death by 26%, regardless of diabetes status 6
• Renal protection: Slows progression of chronic kidney disease and reduces serious renal outcomes 6

Contraindications and Precautions

Key contraindications include:

• Severe renal impairment (eGFR <30 mL/min/1.73 m²) 1
• Type 1 diabetes (risk of diabetic ketoacidosis) 1
• Hypersensitivity to the medication 1

Adverse Effects

Common side effects include:

• Genital mycotic infections (particularly in women) 6, 2
• Urinary tract infections 2
• Volume depletion (especially in elderly or those on diuretics) 1
• Rare but serious: Diabetic ketoacidosis, Fournier's gangrene 1, 2

Unique Properties Compared to Other SGLT2 Inhibitors

• Longer duration of action (18 hours) compared to some other SGLT2 inhibitors 2
• More stable sodium diuresis and reduced blood pressure fluctuations compared to empagliflozin 2
• Less urinary glucose excretion compared to canagliflozin 2

Farxiga represents a significant advancement in medication options, having evolved from a diabetes treatment to an important therapy for cardiorenal protection, with benefits that extend beyond glycemic control to meaningful improvements in mortality and disease progression.