Class V Kmt 4 Inhibitors - 1876 Words

CLASS V: DPP 4 INHIBITORS The DPP 4 inhibitors come in the class of incretin based therapies for type 2 diabetes. The incretin effect is generally blunted in type 2 diabetes patients.16 The two main incretin hormones responsible for blood glucose regulation are GLP-1 (glucagon like peptide-1) and GIP ( glucose dependent insulinotropic peptide). These two hormones are secreted when carbohydrates and fats are consumed and they result in increased glucose dependent insulin secretion or postprandial insulin release and decreased glucagon secretion. Both of these hormones tend to be rapidly metabolized in the circulation by the enzyme DPP 4 (dipeptidyl peptidase). Type 2 diabetes mellitus is characterized by decreased insulin sensitivity and progressive loss of pancreatic beta cell insulin secretion .The DPP 4 inhibitors block the breakdown of naturally occurring GLP 1 by competitively inhibiting the binding of GLP 1 to DPP .The DPP 4 inhibitors decrease the acitivity of the enzyme dipeptidyl peptidase by greater than 80% for up to 24 hours, thereby augmenting the meal related circulating concentrations of both GLP-1 and GIP.19The duration of effect of GLP 1 is thereby increased, thus resulting in a reduction in hepatic glucose output and increase in insulin production. DPP 4 inhibitors currently approved in the US: Generic name Trade name Dosage Combinations Sitagliptin Januvia 25 to 100 mg once daily Janumet( Sitagliptin+Metformin) Saxagliptin Onglyza 2.5 to 5 mg once daily