Linagliptin as add-on therapy for type 2 diabetes - an overview

The pathogenesis of type 2 diabetes (T2D) can result in decreased levels of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which under normal circumstances increase insulin secretion and suppress glucagon release. A new form of drug therapy known as dipeptidyl peptidase 4 (DPP IV) inhibitors has focused on increasing the circulating levels of these "incretin" hormones in order to improve glycemic control in patients with T2D. The DPP IV inhibitors saxagliptin, vildagliptin, linagliptin, alogliptin and sitagliptin function by inhibiting the enzyme DPP IV, which breaks down GLP-1 and GIP, and have had significant success. However, with most DPP IV inhibitors being extensively excreted renally, this is a significant issue, as a large proportion of diabetic patients suffer from renal complications. Linagliptin is a novel DPP IV inhibitor that is excreted primarily by the hepatic route, with little need for dose adjustment in patients with renal impairment. It therefore represents a major advancement in the pharmacotherapy of patients with T2D.