Liraglutide (victoza): the first once-daily incretin mimetic injection for type-2 diabetes.

Abstract

According to the Centers for Disease Control and Prevention (CDC) prevalence data for 2007, diabetes is a chronic and progressive disease that affects nearly 24 million people in the U.S.1 It is projected that by the year 2030, more than 30 million people will have diabetes.2 From 90% to 95% of diagnosed cases are type-2 diabetes, which is characterized by insulin resistance and an altered secretion of pancreatic beta cells, leading to hyperglycemia.1 Diabetes is associated with various microvascular and macrovascular complications that often lead to death. In 2006, diabetes was listed as the seventh leading cause of death in the U.S. The World Health Organization (WHO) predicts that diabetes-related deaths will double between 2005 and 2030 worldwide.1,2 The United Kingdom Prospective Diabetes Study (UKPDS) established the importance of reducing glucose levels to decrease the risk of complications associated with type-2 diabetes.3 Since the publication of that report, more recent studies, such as Action to Control Cardiovascular Risk in Diabetes Trial (ACCORD) and the Veterans Affairs Diabetes Trial (VADT), have re-emphasized the importance of glycemic control and its association with vascular complications.4,5 Although numerous pharmacological agents are available for the management of the disease, type-2 diabetes is controlled in fewer than 50% of patients in the U.S.6 These statistics are alarming; more effort is needed to achieve the recommended American Diabetes Association (ADA) and American Association of Clinical Endocrinologists (AACE) glycosylated hemoglobin (HbA1c) goals of below 7% and 6.5%, respectively.7,8 Research in pharmacological management, in addition to lifestyle modifications, has flourished as a consequence of the complications associated with diabetes. The incretin mimetic class of medications was introduced to the market in 2005 in the form of exenatide (Byetta, Amylin/Lilly), a twice-daily subcutaneous (SQ) injection.9 Incretins—glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)—cause an increase in the amount of insulin released from pancreatic beta cells after meals.10 The incretin effect is defined as a significantly greater insulin stimulatory response after an oral glucose load, compared with an intravenous (IV) glucose infusion when plasma glucose concentrations are equivalent.11 GLP-1 levels are reduced in patients with type-2 diabetes, compared to individuals with normal glucose tolerance.11,12 Thus, product development has focused primarily on GLP-1 for type-2 diabetes. The incretin mimetic liraglutide (Victoza, Novo Nordisk) was approved in the U.S. in January 2010 as an adjunctive therapy to diet and exercise in adults with type-2 diabetes.13 Liraglutide is also approved in Europe and Japan.14