Clinical Medicine Insights: Therapeutics

Diabetes Mellitus (DM) is a chronic disease, with a rapidly increasing worldwide incidence and prevalence. Diabetes accounts for 8% of the US population, according to the United States Centers for Disease Control and Prevention. In terms of individuals, this number comes to a staggering 24 million. In 2007, the total direct medical cost of treating diabetes and its associated complications was $116 billion. More than half of this is spent in treating its complications, both micro and macrovasular. Indirect costs in terms of disability, loss of work or premature mortality amounted to an additional $58 billion. Several trials have shown the benefits of improved glycemic control on microvasular complications and a propensity to reduce macrovasular disease. Furthermore tight glycemic control early in the disease, so called the legacy effect, has shown to reduce mortality. However, these and several other trials have shown the progressive and unrelenting nature of the disease. Reduced efficacies of existing medications over prolonged periods, and continued beta cell dysfunction have lead to unmet glycemic targets. In addition, current antidiabetic medications have significant side effects most of which include hypoglycemia and weight gain. All the above points are rasion d’être that new additional therapies are needed. 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 from 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.