Dipeptidyl Peptidase IV Inhibitors: The Next Generation of New Promising Therapies for the Management of Type 2 Diabetes

Abstract

Type 2 diabetes is a chronic metabolic disease characterized by the presence of both fasting and postprandial hyperglycemia which is a result of pancreas beta-cell dysfunction, deficiency in insulin secretion, insulin resistance and/or increased hepatic glucose production. More recently, the role of other glucoregulatory hormones, including glucagon, amylin, and the gut peptide glucagon-like peptide (GLP)-1, and an increase in the rate of postmeal carbohydrate absorption have also been included as important pathophysiologic defects. Existing anti-diabetes medications are often unefficient at achieving sustained glycemic control because they predominantly address only a single underlying defect. A number of alternative therapies for type 2 diabetes are currently under development that take advantage of the actions of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide on the pancreatic beta-cell. One such approach is based on the inhibition of dipeptidyl peptidase IV (DPP-IV), the major enzyme responsible for degrading the incretins in vivo. DPP-IV exhibits characteristics that have allowed the development of specific inhibitors with proven efficacy in improving glucose tolerance in animal models of diabetes and type 2 diabetic patients. While enhancement of insulin secretion, resulting from blockade of incretin degradation, has been proposed to be the major mode of inhibitor action, there is also evidence that inhibition of gastric emptying, reduction in glucagon secretion, peripheral insulin sensitization and important effects on beta-cell differentiation and survival can potentially preserve beta-cell mass, and improve insulin secretory function and glucose handling in diabetic patients. The present article focuses on the preclinical and clinical data of DPP-IV inhibitors that make it unique therapeutic agents representing the next generation of antidiabetes drugs.

Theeffect of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Disease Risk in Type 2 Diabetes Mellitus

“…Cardiovascular disease (CVD) complications is considered fastest growing health concerns for many diabetic patients [1]. Type 2 diabetes mellitus (T2DM) doubles the risk of major cardiovascular complications for patients with or without established cardiovascular diseases [2][3][4], and causing up to 50-60% of T2DM patients death cases [5][6][7][8].…”

Dipeptidyl peptidase-IV inhibitory activity of dairy protein hydrolysates

“…Type 2 diabetes (T2D) is the most prevalent form of diabetes and is one of the fastest growing health concerns worldwide (Sebokova, Christ, Boehringer, & Mizrahi, 2007). By 2030, it is estimated that the number of people affected with this chronic metabolic disorder will reach 366 million (Wild, Roglic, Green, Sicree, & King, 2004).…”

Comparative Study of Metformin and Vildagliptin for Management of Patients With Type 2 Diabetes Mellitus

“…It acts by increasing the levels of GLP-1 and GIP by inhibiting DPP IV enzyme which is responsible for degradation of GLP-1 and GIP. 13 Vildagliptin caused more reduction of FPG & PPG but similar reduction of HbA1c after 12 weeks of therapy as compared to that of metformin.…”