Subcutaneous exenatide extended-release (ER; Bydureon™; also known as exenatide once weekly), a glucagon-like peptide-1 receptor agonist, provides a convenient, simple, once-weekly regimen that is approved in adult patients with type 2 diabetes as adjunctive monotherapy to diet plus exercise (in the US; not as first-line therapy) and/or as combination therapy with specific oral antihyperglycaemic drugs (OADs) in patients with inadequately controlled type 2 diabetes despite treatment with these OADs (US and Europe). This article reviews the clinical efficacy and tolerability of exenatide ER in the treatment of adult patients with type 2 diabetes and gives a brief overview of its pharmacological properties. In several short-term (24-30 weeks) well designed trials, adjunctive subcutaneously injectable exenatide ER once weekly, as monotherapy or in combination with OADs, significantly improved glycaemic control, bodyweight and some surrogate markers of cardiovascular risk in adult patients with inadequately controlled type 2 diabetes despite diet and exercise and/or treatment with OADs. Furthermore, the beneficial effects of adjunctive exenatide ER therapy were sustained in extension studies of up to 3 years of treatment. Overall, the intensity of glycaemic control with exenatide ER was generally better than that observed with the exenatide immediate-release formulation (twice daily), sitagliptin or insulin glargine. Exenatide ER was shown to be noninferior to metformin in terms of glycaemic efficacy, but did not meet the criteria for noninferiority versus liraglutide. In treatment-naive patients, exenatide ER treatment did not meet noninferiority criteria versus pioglitazone, whereas in treatment-experienced patients, exenatide ER provided better glycaemic control than pioglitazone. Improvements in glycaemic control with exenatide ER and, in general, with other antihyperglycaemic agents were reflected in significant improvements from baseline in treatment satisfaction and health-related quality-of-life measures. Exenatide ER was generally well tolerated in patients participating in these trials, with most treatment-emergent adverse events being of a gastrointestinal nature, of mild to moderate severity, transient and of a similar nature and incidence to those occurring with the exenatide immediate-release formulation. Thus, exenatide ER is a useful option for the treatment of type 2 diabetes, particularly in patients where bodyweight loss is an essential aspect of the individual patient's management.