Emerging DPP-4 inhibitors: focus on linagliptin for type 2 diabetes

The first dipeptidyl-peptidase-IV (DPP-4) inhibitor for the treatment of type 2 diabetes became available in 2006. Since then, the number of DPP-4 inhibitors has increased and DPP-4 inhibitors have developed into an important drug class. DPP-4 inhibitors act by increasing endogenous GLP-1 and GIP concentrations. Via this mechanism, insulin secretion is glucose-dependently stimulated and glucagon secretion inhibited. This results in a low risk for hypoglycemia. Furthermore, DPP-4 inhibitors are weight-neutral. Linagliptin is a novel DPP-4 inhibitor that, in contrast to the other members of this drug class, is eliminated by a biliary/hepatic route rather than by renal elimination. This property allows the use of linagliptin in type 2 diabetic patients with normal kidney function as well as in patients with renal insufficiency without dose adjustments. In comparative clinical studies, linagliptin was noninferior to other established antidiabetic agents, especially to metformin and sulfonylurea. It showed a superior safety profile over glimepiride regarding hypoglycemia, weight gain, a composite cardiovascular endpoint, and stroke. This review gives an overview on the efficacy and safety of linagliptin in comparison to the classical oral antidiabetic drugs as well as to the other DPP-4 inhibitors.