Clinical Medicine Insights: Therapeutics

Type 2 diabetes mellitus (T2DM) is a chronic, progressive metabolic disorder that is associated with long-term microvascular (retinopathy, neuropathy and nephropathy) and macrovascular (myocardial infarction, stroke, peripheral arterial disease) complications. Both the prevalence of T2DM and the cost of its long-term complications have driven the focus and emphasis on treatments aimed at reducing hyperglycemia and controlling hypertension and dyslipidemia while minimizing hypoglycemia and weight gain. Exenatide twice daily, the first GLP-1R agonist approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMEA), has been shown to reduce hemoglobin A1C, lower fasting and postprandial plasma blood glucose concentrations as well as reduce body weight without causing significant hypoglycemia. However, its current formulation requires twice daily subcutaneous injections and does not provide continuous GLP-1R activation. Therefore, a long-acting release form of exenatide has been developed for use as a once-weekly injection, providing for convenient administration and continuous GLP-1R activation. This review covers the currently published data on this new formulation including mechanism of action, pharmacokinetics, efficacy and comparison trials to other commonly used anti-diabetic agents.