Exenatide is the first drug in the incretin mimetic class and is indicated for treatment of type 2 diabetes mellitus. Although structurally similar to the native glucagon-like peptide, this synthetic form has a much longer duration of action. Randomized trials have shown exenatide to be efficacious in improving glycemic control when combined with either metformin or a sulfonylurea. The dose is initially 5 mcg subcutaneously twice daily and may be titrated to 10 mcg subcutaneously twice daily to achieve better diabetes management. Nausea, vomiting, and diarrhea were the most common adverse events reported with exenatide therapy. Exenatide is not associated with hypoglycemia, which may provide advantages over adding insulin to a sulfonylurea or metformin. The American Diabetes Association estimates that 17 million people in the USA have type 2 diabetes (1). Currently, the first-line oral agents for type 2 diabetes are metformin and sulfonylureas. Other therapeutic options include thiazolidinediones and insulin. Despite best efforts, monotherapy or combination therapy of metformin and a sulfonylurea fails in many patients. This presents a problem because many second- and third-line agents may cause weight gain, hypoglycemia, and other adverse effects. Exenatide (Byetta) is the first in a new class of incretin peptide mimetics (glucagon-like polypeptide-1 [GLP-1] receptor agonists) available in the USA. It was approved by the Food and Drug Administration (FDA) in April 2005 for adjunctive glycemic control in patients with type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of metformin and a sulfonylurea (2).