Dapagliflozin (Farxiga) is now approved to reduce the risk of declining kidney function, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease with or without type 2 diabetes. The drug was originally approved in 2014 to improve glycemic control in adults with type 2 diabetes and received approval in 2020 to reduce the risk of cardiovascular death and hospitalization in adults with heart failure and reduced ejection fraction with or without diabetes.
Dapagliflozin is an oral once-daily sodium-glucose cotransporter 2 inhibitor that reduces the reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby promoting glucose excretion in the urine. With less reabsorption of glucose, glycated hemoglobin is decreased. Dapagliflozin also reduces the reabsorption of sodium and increases sodium delivery to the distal tubule.
According to the Centers for Disease Control and Prevention, kidney diseases are the ninth leading cause of death in the United States and approximately 37 million U.S. adults (more than one in seven) have chronic kidney disease, though many are undiagnosed.1 Chronic kidney disease can be caused by diseases or conditions such as type 1 or type 2 diabetes, hypertension, glomerulonephritis, interstitial nephritis, prolonged obstruction of the urinary tract, vesicoureteral reflux, recurrent kidney infection, and polycystic kidney disease.2 Cardiovascular disease can increase the risk as well as be a complication of chronic kidney disease.
The recent new indication for dapagliflozin was based on findings from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, a phase 3, international, multicenter, randomized, double-blind clinical trial of 4,304 patients with stage 2 to 4 chronic kidney disease, glomerular filtration rates between 25 and 75 mL/min, and elevated urinary albumin excretion.3 Findings indicated that dapagliflozin, in addition to standard care with either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, reduced the relative risk of the primary composite end point of worsening renal function, onset of end-stage kidney disease, or risk of cardiovascular or renal death by 39% compared with placebo. Dapagliflozin also reduced the relative risk of death from any cause by 31% compared with placebo. The drug was equally effective in people with and without diabetes. The DAPA-CKD clinical trial was ended early due to the efficacy of dapagliflozin. Adverse effects of dapagliflozin were similar to those observed in previous studies.
Dapagliflozin was not studied and is not recommended in patients with autosomal dominant or recessive polycystic kidney disease or in patients who require or have recently used immunosuppressive therapy to treat kidney disease. Treatment with dapagliflozin is contraindicated if patients have a history of serious hypersensitivity reactions to the drug or if they receive dialysis.
To read the FDA News Release about dapagliflozin's approval, see http://www.fda.gov/news-events/press-announcements/fda-approves-treatment-chroni.
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