Medicinal Chemistry and Applications of Incretins and DPP-4 Inhibitors in the Treatment of Type 2 Diabetes Mellitus



Mohamed Lotfy1, Jaipaul Singh2, Huba Kalász3, Kornelia Tekes4, Ernest Adeghate*, 5
1 Department of Biology, Faculty of Science, UAE University
2 School of Forensic and Investigative Science and School of Pharmacy and Biomedical Science, University of Central Lancashire, Preston PR1 2HE, England, UK
3 Huba Kalász, Department of Pharmacology and Therapeutics, Semmelweis University, Hungary
4 Kornelia Tekes, Department of Pharmacodynamics, Semmelweis University, Hungary
5 Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, UAE


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© Lotfy et al.; Licensee Bentham Open.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates; Fax: +971-3-7672033; E-mail: eadeghate@uaeu.ac.ae


Abstract

Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 200 million people worldwide. Approximately 90% of all diabetic patients suffer from Type 2 diabetes mellitus (T2DM). The world's economy coughs out billions of dollars annually to diagnose, treat and manage patients with diabetes. It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) can preserve the morphology and function of pancreatic beta cell. In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. This review examines the medicinal chemistry and roles of incretins, specifically, GLP-1 and drugs which can mimic its actions and prevent its enzymatic degradation. The review discussed GLP-1 agonists such as exenatide, liraglutide, taspoglutide and albiglutide. The paper also identified and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP-4), the enzyme responsible for the rapid degradation of GLP-1. These DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin and many others which are still in the experimental phase.

Keywords: Incretins, DPP-4 inhibitors, type 2 diabetes, medicinal chemistry.