Advances in New Drugs for Diabetes Treatment: GLP-1 Mimetics and DPP-4 Inhibitors

The dramatic rise in the prevalence of obesity and diabetes is associated with increased mortality, morbidity as well as public health care costs worldwide. The need for new effective and long-lasting drugs is urgent. Recent research has focused on the role of incretin in the maintenance of glucose homeostasis through their actions on both α- and β- cell function. Moreover, increased knowledge of the pathophysiology of diabetes has contributed to the development of novel drugs, including injectable glucagon-like peptide-1 (GLP-1) mimetics, and oral dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1 agonists mimic the effect of this incretin, whereas DPP-4 inhibitors prevent the inactivation of the endogenously released hormone. GLP-1 appears to be involved in both peripheral and central pathways mediating satiety. Clinical trials have shown that two GLP-1 receptor agonists exenatide and liraglutide have a weight-lowering potential in non-diabetic obese individuals. Furthermore, they may also hold a potential in preventing diabetes as compared to other weight loss agents. Both agents offer an effective alternative to the currently available hypoglycaemic drugs but further evaluation is needed to confirm their clinical roles and safety. The purpose of this review is to summarize the background of the incretin, and the roles and side effects of the GLP-1 agonists and DPP-4 inhibitors in clinical trials. In addition, up-to-date literature on GLP-1 agonists and DPP-4 inhibitors based clinical therapies will be summarized with a special mention of their weightlowering properties. In conclusion, the incretin impairment, which seems to exist in both obesity and diabetes, may link these two pathologies and underlines the potential of incretin based therapies in the prevention and treatment of obesity and diabetes.

Keywords: Alogliptin, DPP-4 Inhibitors, Exenatide, GLP-1 Agonists, Incretin, Linagliptin, Liraglutide, Saxagliptin, Sitagliptin, Vildagliptin.