Newer drugs in Treatment of Type 2 Diabetes

Incretins

Incretins are gastrointestinally secreted insulinotropic hormones that play an important role in glucose homeostasis as they are involved in augmentation of -cell secretion of insulin and in suppression of glucagon secretion by the cell. The incretin effect refers to the augmented release of insulin that is observed from oral ingestion of glucose when compared with intravenous glucose challenge, even though the glucose concentration achieved in plasma may be equivalent. There are two different gut hormones that are mainly responsible for the incretin effect, which may include glucose-dependent insulinotropic peptide and GLP-1. In contrast to glucose-dependent insulinotropic peptide, GLP-1 maintains a glucoregulatory function in individuals both with and without diabetes. For this reason, GLP-1 was identified as a potential therapeutic agent for diabetes treatment.

One of the major concerns for GLP-1 that limited clinical applicability is the rapid enzymatic degradation by DPP-4 and as such, requires continuous intravenous or subcutaneous infusion. To address the problem, two research approaches have been attempted. One is to modify the molecule to resist or delay degradation. Agents such as exenatide and liraglutide are GLP-1 receptor agonists that are resistant to DPP-4 inhibition. A second approach has been to inhibit endogenous DPP-4 activity, thus prolonging the circulating half-life of native GLP-1. Agents in the DPP-4 inhibitor class are represented by vildagliptin and sitagliptin