Adapting the GLP-1-Signaling System to the Treatment of Type 2 Diabetes

Glucagon-like peptide-1 (GLP-1) may contribute to the decreased incretin effect characterizing type 2 diabetes. Multiple actions other than insulin secretion stimulation give to GLP-1 a highly desirable profile for an antidiabetic agent. To overcome the need for continuous infusion of the native compound, which is rapidly degraded by dimethyl-peptidyl-peptidase-IV (DPP-IV), analogues with low affinity for this protease have been developed. A second major strategy is represented by DPP-IV inhibitors that act to increase endogenous GLP-1. On the basis of the promising results in clinical trials, the incretin-based therapy may offer an useful option for diabetes management.