Farxiga (Dapagliflozin) Drug Classification
Farxiga (dapagliflozin) is an SGLT2 inhibitor (sodium-glucose cotransporter-2 inhibitor), a class of medication that works by blocking glucose reabsorption in the kidneys, leading to urinary glucose excretion. 1
Mechanism of Action
- Dapagliflozin selectively inhibits SGLT2 in the proximal renal tubules, preventing reabsorption of filtered glucose and promoting urinary glucose excretion. 1
- The drug also reduces sodium reabsorption and increases sodium delivery to the distal tubule, which lowers cardiac pre- and afterload, downregulates sympathetic activity, and decreases intraglomerular pressure through increased tubuloglomerular feedback. 1
- This mechanism is independent of insulin secretion or action, making it complementary to other antidiabetic therapies. 2, 3
FDA-Approved Indications
Dapagliflozin has four distinct FDA-approved uses:
- Type 2 diabetes mellitus (approved 2014): For glycemic control as monotherapy or combination therapy 4, 2
- Heart failure with reduced ejection fraction (HFrEF) (approved 2020): To reduce cardiovascular death and hospitalization for heart failure, regardless of diabetes status 5, 6
- Chronic kidney disease (approved 2021): To reduce risk of declining kidney function, kidney failure, cardiovascular death, and hospitalization for heart failure 5, 7
- Heart failure with preserved ejection fraction (HFpEF) (approved 2023) 4
Clinical Evidence Supporting SGLT2 Inhibitor Class Effects
- The DAPA-HF trial demonstrated a 26% reduction (HR 0.74,95% CI 0.65-0.85) in the composite outcome of worsening heart failure or cardiovascular death in patients with HFrEF, with benefits consistent regardless of diabetes status. 8, 5
- In the DECLARE-TIMI 58 trial, dapagliflozin showed a 27% reduction in hospitalization for heart failure in patients with type 2 diabetes. 8
- The DAPA-CKD study demonstrated a 39% reduction in the composite of kidney disease progression, end-stage renal disease, and cardiovascular or renal death. 5
- Multiple cardiovascular outcomes trials (EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58, CREDENCE) consistently show SGLT2 inhibitors as a class reduce heart failure hospitalizations by 27-39%. 8
Pharmacokinetics
- Oral bioavailability is 78% with maximum plasma concentration reached within 2 hours. 1
- The drug has an 18-hour duration of action with minimal cytochrome P450-mediated metabolism. 4
- Metabolism occurs primarily via UGT1A9, producing an inactive glucuronide metabolite. 1
- Approximately 91% protein bound, with binding unaffected by renal or hepatic impairment. 1
Key Safety Considerations
- Common adverse effects include genital mycotic infections (particularly in women), urinary tract infections, and volume depletion. 8, 5
- Low risk of hypoglycemia when used as monotherapy, though risk varies with background therapy. 5, 2
- Contraindicated in type 1 diabetes and end-stage chronic kidney disease. 4
- Rare but serious risk of Fournier's gangrene. 4
- For glycemic control in patients without established cardiovascular disease, not recommended when eGFR is less than 45 mL/min/1.73 m². 1
- Efficacy and safety trials did not enroll patients with eGFR less than 25 mL/min/1.73 m² or on dialysis. 1