Development of new incretin drugs: Promising therapies

Abstract

New agents are being added to the armamentarium of drugs used for the treatment of diabetes mellitus. Today, extensive research is being conducted on incretin hormones. Important among them are, Glucagon like peptide-1 (GLP-1) and Glucose dependent insulinotropic peptide (GIP). The gastrointestinal tract secretes these hormones in response to the ingestion of nutrients. These hormones increase secretion of insulin, decrease secretion of glucagon, decrease gastric emptying time (only by GLP-1). In addition, they decrease body weight and prevent development of resistance to insulin. They are rapidly degraded by dipeptidyl peptidase (DPP-IV) enzyme. Analogs of GLP-1 and GIP and inhibitors of DPP-IV are being synthesised. Exenatide, a synthetic analog of GLP-1, has recently been approved by the FDA, USA for use in patients with type 2 diabetes who have sub optimal control despite treatment with metformin and / or a sulfonylurea. Other GLP-1 analogs under clinical trial are: NN2211, CJC1131, and Albugon. No analog of GIP and inhibitor of DPP-IV have been approved by the FDA for clinical use till now. Vildagliptin, an inhibitor of DPP-IV, is under phase 2 clinical trials. The incidence of hypoglycemia is less with these incretin mimetics and inhibitors of DPP-IV. Minimal gastrointestinal side effects are seen. Analogs of GLP-1 have to be given subcutaneously, while inhibitors of DPP-IV can be given orally. There is a need to synthesise long acting analogs of GLP-1 and selective inhibitors of DPP-IV.