Farxiga Drug Classification
Farxiga (dapagliflozin) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor. 1
Mechanism of Action
SGLT2 inhibitors work by blocking glucose reabsorption in the proximal tubule of the kidney, leading to increased urinary glucose excretion (glucosuria). 2 The SGLT2 protein is responsible for up to 90% of filtered glucose reabsorption in the renal nephron. 2 By competitively binding to these renal SGLT2 cotransporters, dapagliflozin prevents both glucose and sodium reabsorption. 3
Clinical Indications
Dapagliflozin has multiple FDA-approved indications beyond glycemic control:
Type 2 diabetes mellitus: Improves glycemic control as an adjunct to diet and exercise, with HbA1c reductions of 0.5-0.7% at doses of 5-10 mg. 4, 2
Heart failure with reduced ejection fraction (HFrEF): Reduces risk of cardiovascular death and hospitalization for heart failure in adults with HFrEF, regardless of diabetes status. 4, 1
Heart failure with preserved ejection fraction (HFpEF): Reduces cardiovascular death, hospitalization for heart failure, or urgent heart failure visits. 5, 1
Chronic kidney disease: Reduces risk of sustained eGFR decline ≥50%, end-stage kidney disease, and cardiovascular or renal death in patients with albuminuric kidney disease. 6, 1
Distinguishing Features Within the SGLT2 Inhibitor Class
Dapagliflozin is among the most selective SGLT2 inhibitors, along with empagliflozin and ertugliflozin, with minimal SGLT1 inhibition. 7 This contrasts with canagliflozin, which has greater SGLT1 inhibitory activity and affects intestinal glucose absorption. 7
The drug has an 18-hour duration of action with minimal cytochrome P450 metabolism, contributing to stable pharmacokinetic effects. 3 Compared to empagliflozin, dapagliflozin may have more extended effects leading to stable sodium diuresis and reduced blood pressure fluctuations, though it produces less urinary glucose excretion than canagliflozin. 3
Dosing and Administration
The standard dose is 10 mg once daily by mouth. 4, 8 No dose titration is required for cardiovascular or renal benefits, as this represents the lowest dose tested in outcomes trials. 4 The glucose-lowering effect diminishes at eGFR <45 mL/min/1.73 m², but the medication should be continued for cardiovascular and kidney benefits until dialysis or transplantation. 8