The Food and Drug Administration (FDA) has approved dapagliflozin (Farxiga) as a new sodium–glucose cotransporter 2 (SGLT2) inhibitor to control type 2 diabetes. Like the first SGLT2 inhibitor, canagliflozin (Invokana), which was approved in 2013 (see Drug Watch, July 2013), dapagliflozin produces osmotic diuresis by blocking SGLT2; because the drug prevents renal reabsorption of glucose, it lowers blood glucose levels. In clinical trials, long-term control of glucose improved in patients taking dapagliflozin, as evidenced by lowered glycated hemoglobin levels. Dapagliflozin cannot be used in the treatment of type 1 diabetes or diabetic ketoacidosis. It is taken once daily with or without food.
There are several warnings and precautions listed in dapagliflozin's labeling. Many are similar to the warnings in canagliflozin's labeling. First, the drug can produce hypotension because it decreases intravascular volume. It can alter renal function, too, as evidenced by an increase in the serum creatinine concentration and a decrease in the estimated glomerular filtration rate (eGFR). Hypoglycemia is possible in certain patients; in patients concurrently taking insulin or an insulin secretagogue (a drug that encourages the β cells of the pancreas to secrete insulin) such as glyburide (DiaBeta and others), glipizide (Glucotrol), repaglinide (Prandin), and nateglinide (Starlix), a lower dosage of the insulin secretagogue may be warranted to reduce the risk of hypoglycemia with dapagliflozin use. Low-density lipoprotein cholesterol levels may also increase while a patient is taking dapagliflozin. Another labeled warning is that the drug can cause genital fungal infections in female patients. Finally, dapagliflozin carries a warning that it may increase the risk of bladder cancer, although the number of bladder-cancer cases occurring during clinical trials was too low to determine whether they were related to dapagliflozin use. The drug needs to be used cautiously in patients with a history of bladder cancer.
Because of these concerns, the FDA is requiring six postmarketing studies of dapagliflozin:
* a cardiovascular outcomes trial to evaluate dapagliflozin's cardiovascular risk in patients with a high baseline risk of cardiovascular disease
* a double-blind, randomized controlled assessment of bladder-cancer risk in patients enrolled in the above trial
* an animal study evaluating the roles of dapagliflozin-induced urinary flow and rate changes and changes in urinary composition in bladder-tumor promotion in rodents
* two clinical trials to assess the pharmacokinetics, efficacy, and safety of dapagliflozin in children 10 to 17 years of age
* a five-year assessment and analysis of all spontaneous reports (domestic and international) of serious hepatic abnormalities and pregnancy outcomes in patients treated with dapagliflozin
The most common adverse effects—genital yeast infections (in female patients), nasopharyngitis, and urinary tract infections—are generally not serious. Nurses prescribing or caring for patients prescribed dapagliflozin should confirm that patients have adequate renal function, as assessed using the eGFR, prior to the start of therapy. The patient's eGFR should be 60 mL/min/1.73 m2 (body surface area) or higher in order for therapy to begin. Renal function should also be assessed periodically throughout therapy; if the eGFR falls below 60 mL/min/1.73 m2, dapagliflozin therapy should be discontinued. If hypovolemia is present, it should be corrected prior to the start of dapagliflozin therapy. Nurses should carefully assess older adults, patients with renal impairment, those with a low systolic blood pressure, and those taking diuretics for hypotension; these conditions increase the patient's risk of hypotension with dapagliflozin therapy. Nurses should confirm that patients don't have active bladder cancer before therapy with dapagliflozin is started. Nurses should instruct patients to assess their blood glucose level regularly while taking dapagliflozin to check for hypoglycemia.
Complete FDA prescribing information can be found online at http://1.usa.gov/1dBzUOa.