Type 2 diabetes is characterized by progressive insulin resistance and pancreatic beta-cell dysfunction resulting in key defects in insulin secretion and function . Ultimately, this leads to difficulties in controlling hyperglycemia, which has been associated with microvascular and macrovascular complications [2, 3]. Because lowering of A1C has been shown to reduce the risk of long-term microvascular - and possibly macrovascular - complications [3–7], a target A1C level of <7% has been recommended by the American Diabetes Association (ADA)  for patients with diabetes; the American Association of Clinical Endocrinologists and the American College of Endocrinology (AACE/ACE)  have recommended a more stringent A1C target of ≤6.5%. Thus, the overall goal for the treatment of type 2 diabetes is to reduce A1C to as near normal levels as possible, with considerations for the risk of hypoglycemia and the risk of comorbidites that are common in type 2 diabetes, including obesity, dyslipidemia, and hypertension.
Treatment of type 2 diabetes often begins with lifestyle modifications, but as the disease progresses, most patients require pharmacotherapy. However, many patients with type 2 diabetes do not maintain the recommended glycemic targets over time with traditional therapies and must transition to combination therapy and/or increasing doses of insulin as their glycemic control deteriorates [5, 6, 10, 11]. Furthermore, the use of many antihyperglycemic agents can be accompanied by increased hypoglycemia, weight gain, and a persistence of elevated postprandial glucose excursions . To address the need for more comprehensive treatment of type 2 diabetes, recent algorithms developed by the AACE and ADA/European Association for the Study of Diabetes have recommended the use of glucagon-like peptide-1 (GLP-1) receptor agonists (monotherapy or combination therapy) on the basis of their effective glycemic control, weight loss effects, low rates of hypoglycemia, and overall safety profiles, and particularly for use in patients for whom hypoglycemia is especially undesirable or promotion of weight loss is a major consideration [2, 9, 11].
Exenatide is a potent GLP-1 receptor agonist with multiple glucoregulatory effects for the treatment of type 2 diabetes [12–18]. Treatment with exenatide twice daily (BID) enhances glucose-dependent insulin secretion, reduces inappropriate elevations in glucagon secretion, slows gastric emptying, and reduces body weight in a substantial proportion of treated patients [13–19]. Furthermore, the clinical effects of exenatide are sustained over time, as shown in long-term studies of exenatide BID [19, 20].
The sustained-release formulation of exenatide, exenatide once-weekly (QW), allows for continuous drug release over time, resulting in sustained therapeutic levels of exenatide - and thus, 24-hour glycemic control - with a single weekly injection [21, 22]. Providing continuous GLP-1 receptor agonism has emerged as an increasingly important opportunity in treating type 2 diabetes, as evidence indicates that controlling both fasting and postprandial hyperglycemia is essential to providing comprehensive glycemic control [23, 24].
The DURATION-1 trial was designed to compare the safety and efficacy of exenatide BID with exenatide QW in patients with type 2 diabetes. This 2-stage protocol consisted of a randomized, open-label comparison of exenatide QW and exenatide BID for 30 weeks, followed by an open-ended assessment period in which all patients received exenatide QW. The results from the 30- and 52-week assessment periods have previously been reported [25, 26]. The objective of this report is to describe the safety and efficacy of 2 years of exenatide QW treatment in patients with type 2 diabetes.