Emerging role of dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin in the management of type 2 diabetes

Abstract

Diabetes mellitus (DM) is one of the most common chronic disorders, with increasing prevalence worldwide. Type 2 diabetes (T2DM), a multifaceted disease involving multiple pathophysiological defects, accounts for nearly 85-95% of total reported cases of DM. Chances of developing T2DM are increased by obesity and physical inactivity and are augmented further with age. Two most important unmet needs associated with the management of T2DM are the lack of lasting efficacy in reducing hyperglycemia and failure to target primary causes. Different classes of Oral Hypoglycemic Agents (OHA's) with nearly equipotent efficacy are now available targeting the different pathophysiologic factors contributing to T2DM; however, almost all of them are associated with one or the other kind of adverse effect. Several studies have found that certain diabetes drugs may carry increased cardiovascular (CV) risks compared to others. The new approach in management of T2DM based upon the effects of incretin hormones; Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Vildagliptin is a drug from a new class of medications called dipeptidyl peptidase IV (DPP4) inhibitors. By inhibiting DPP-4, vildagliptin causes an increase in GLP-1, an intestinal hormone that aids in glucose homeostasis and insulin secretion. Vildagliptin has a half-life of about 90 minutes; however, > or = 50% of DPP4 inhibition continues for more than 10 hours, allowing for once- or twice-daily dosing. Clinical trials have shown that vildagliptin is effective in significantly lowering glycosylated hemoglobin (HbA1c), fasting plasma glucose, and prandial glucose levels. beta-cell function may also be improved. The drug has placebo like tolerability and rate of hypoglycemia events. Vildagliptin expands non-injectable treatment options available for management of T2DM patients, who are poorly controlled with monotherapy.