Abstract 21 V1 I2

Management of T2DMin obese patients is particularly challenging as treatment with the majority of glucose-lowering agents results in weight gain. Thus, the development of a therapeutic option which could improve glycemic control without weight gain or hypoglycemia, such as the glucagon-like peptide-1 (GLP-1) analog exenatide, is a welcome addition to the currently available therapies in the management of T2DM. With recognition and better understanding of the role of incretin hormones in T2DM, exenatide was developed and introduced into clinical practice in 2005. Both randomized controlled trials and retrospective observational studies have shown that treatment with exenatide not only improves glycemic control, with a low risk of hypoglycemia, but also results in concurrent weight loss and the additional benefit of improvement in cardiovascular risk factors.

Exenatide is a unique agent which can effectively control blood glucose levels in type 2 diabetes mellitus without producing dangerous adverse effects. In addition, it can lower body weight which is very essential for the treatment of obese type 2 diabetes mellitus patients. Since it can delay the destruction of islet beta-cells, type 2 diabetes mellitus patients are not rapidly converted to type 1 diabetes mellitus and ultimately appearance of complications of the disease is halted or delayed. In addition, current antidiabetic medications have significant side effects most of which include hypoglycemia and weight gain. Recently, new classes of agents targeting the incretin system have become available. These can be divided into two broad categories; glucagon like peptide-1 (GLP-1) agonists/analogs (exenatide, liraglutide), and dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin, vildagliptin, and Saxagliptin (undergoing phase 3 trials)).

Exenatide, a 39-amino acid peptide produced in the salivary gland of the Gila monster lizard, is a GLP-1 agonist. It is the first of its class approved for use as adjunctive therapy, in patients with Type 2 diabetes mellitus (T2DM). Current data suggests that exenatide, in combination with metformin, glyburide, or a glitazone, results in significant reductions in fasting and postprandial plasma glucose and hemoglobin A1c (HbA1c). Apart form gastrointestinal side effects, exenatide is relatively well tolerated and does not cause hypoglycemia when used alone. Additionally, the drug serves to promote moderate weight loss. The authors aim to provide a comprehensive overview of exenatide, detail its mechanism of action, and discuss its role in the present day treatment of patients with T2DM.

Keywords: Antidiabetic agent, Exenatide, incretin-mimetic peptide Hormone, T2DM