OBJECTIVES: To describe the Exenatide Observational Study (ExOS) and patients initiating exenatide therapy in a real-world clinical practice setting. METHODS: ExOS is a prospective, single-arm, multicenter, observational study to assess the effectiveness of up to 24 months of exenatide therapy in patients with type 2 diabetes (T2D). Patients with T2D >/=18 years of age, who initiated exenatide therapy, were eligible. The primary effectiveness endpoint is achieving or maintaining hemoglobin A1C of 2 (10.2%)], or some form of insulin +/-OADs (19%), and >/=50% were on a cholesterol-lowering drug(s) +/- antihypertensive medication(s). The single-arm design of this study is a limitation; however, the overall objective of the ongoing study is to observe patients on exenatide therapy over time, comparing their status at endpoint to baseline, rather than to make comparisons among different drug therapies. CONCLUSIONS: Patients treated with exenatide tended to be obese, middle-aged women on various combinations of OADs and/or insulin who often had hypertension and/or dyslipidemia. Further planned analyses will provide the largest sample of prospective data on outcomes of exenatide therapy for up to 24 months in this usual-care population.