Place in Therapy
Dapagliflozin is the most widely studied agent in a new class of drugs that have the ability to lower plasma glucose by promoting glucosuria. With this distinctive mechanism of action, dapagliflozin provides sustained glucose lowering and addresses the shortcomings of many currently available OADs: weight gain, fluid retention, gastrointestinal effects, and hypoglycemia. More important, dapagliflozin might interfere with the pathogenic defects of type 2 diabetes (i.e., β-cell apoptosis and insulin insensitivity), an effect that some other OADs may accelerate.[16,74] Drugs are often underutilized in prediabetic and glucose-tolerant patients with a family history of diabetes, where it is said that deleterious effects on β-cell functioning are present.[75,76] Dapagliflozin may serve as a useful drug in these subsets of patients given that it has an insulin-independent mechanism of action, although clinical studies are needed to validate dapagliflozin's ability to reduce the progression to diabetes.
Dapagliflozin also provides reductions in total body weight and blood pressure. These differentiating features may render it beneficial in patients with cardiovascular disease; however, long-term clinical trials and postmarketing experience are under way and will assess dapagliflozin's cardiovascular profile. Current literature in both treatment-naïve and -experienced patients suggests that clinicians will likely be able to use dapagliflozin as monotherapy or add-on therapy. Strong clinical programs that assess the long-term safety and efficacy of dapagliflozin are ongoing and will attempt to resolve the following important therapeutic issues: its adverse-effect profile (particularly urogenital infections), antiobesity and blood pressure-lowering effects, and reversibility of β-cell dysfunction.
Pharmacotherapy. 2012;32(1):80-94. © 2012 Pharmacotherapy Publications