Incretin-Based Therapies for the Treatment of Type 2 Diabetes – DPP-4 Inhibitors and Incretin Mimetics

Abstract

The current treatment options for type 2 diabetes do not achieve the glycemic goals. Improving islet function by incretin hormone action is a novel and attractive therapeutic approach. There are two different approaches to utilize incretin action in the treatment of type 2 diabetes: dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of the incretins glucagon-like peptide-1 (GLP-1) and glucosedependent insulinotropic peptide. The DPP-4 inhibitors sitagliptin and vildagliptin are orally active and have been shown to be efficacious and safe. They reduce hemoglobin A1c (HbA1c), fasting and postprandial glucose by glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion. They are weight neutral. Indirect measures show an improvement of -cell function. DPP-4 inhibitors do not cause a higher rate of hypoglycemia in comparison to metformin or placebo. The second option is using GLP-1 receptor agonists, called incretin mimetics. Exenatide is available for subcutaneous injectable therapy, liraglutide is in phase III clinical trials. Both compounds are peptides. They reduce HbA1c sustainedly, lead to weight loss and also show an improvement in -cell function in man and an increase in -cell mass in animal models.