Exploring the pharmacotherapeutic options for treating type 2 diabetes.

There has been a dramatic increase in the prevalence of the most common form of diabetes, with approximately 14.6 million diagnosed and 6.2 million undiagnosed cases of type 2 (non-insulin-dependent) diabetes in the United States since 2005. If diabetes is not diagnosed early and managed properly, patients are at greater risk for microvascular and macrovascular complications, such as nerve damage, heart disease, blindness, and kidney damage. The pathogenesis of type 2 diabetes includes impaired insulin secretion, increased hepatic and muscle/fat insulin resistance, and increased glucagon secretion. Problems commonly associated with type 2 diabetes and consequent hyperglycemia are weight gain, hypertension, and dyslipidemia. The natural progression of type 2 diabetes involves increased insulin deficiency as a result of decreased beta cell function over time, which can raise glycosylated hemoglobin to dangerous levels and consequently increase the risk of death. Lifestyle modifications (eg, diet changes and increased physical activity) remain the cornerstone of early treatment, but glycemic control may worsen despite behavior changes and treatment with oral hypoglycemic agents. Historically, upon failure to maintain glucose levels with exercise and oral medication, insulin was the second-line treatment option. Current treatment algorithms include a new class of agents, incretin mimetics, such as the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide. Exenatide mimics the actions of the hormone GLP-1 that occurs naturally in the gastrointestinal tract and has emerged as an efficacious therapy adjunct to 1 or more oral hypoglycemic agent(s).