Article Summary Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes. Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG, for the GWAA Study Group. Ann Intern Med. 2005;143:559-569. Objective: To assess and compare the effects on glycemic control of exenatide and insulin glargine in patients with type 2 diabetes mellitus who have not achieved such control with the use of metformin and a sulfonylurea. Methods: A total of 551 patients between 30 and 75 years of age were randomly assigned to a 26-week multicenter, open-label, controlled clinical trial at 82 outpatient centers in 13 countries. These patients had been diagnosed with type 2 diabetes and had experienced inadequate glycemic control with the use of combined therapy with metformin and a sulfonylurea. In this study, exenatide (twice daily) or insulin glargine (once a day) was added to the treatment regimen so that effects of these agents in improving glycemic control could be assessed and compared. The primary efficacy variable was the change in hemoglobin A1c level from baseline. Other continuous variables analyzed included body weight, fasting serum glucose level, and self-monitored blood glucose level. Results: Findings included a reduction in hemoglobin A1c of 1.11% from baseline to week 26 in both treatment groups. The percentage of patients whose hemoglobin A1c reached a target level equal to or less than 7% at week 26 was also similar (46% for exenatide, 48% for insulin glargine). Those treated with insulin glargine gained weight (1.8 kg) throughout the trial; however, the exenatide treatment group demonstrated progressive weight reduction (2.3 kg) during this time. Both treatments decreased fasting plasma glucose levels, but the reduction was significantly greater with insulin glargine (P<0.001) than with exenatide. Mean daily self-monitored blood glucose levels at week 26 were similar in the exenatide and insulin glargine treatment groups (10.2 mmol/L and 10.1 mmol/L, respectively). Adverse events, which included nausea and vomiting, back pain, and dizziness, were more common among the group receiving exenatide. Conclusions: In patients with type 2 diabetes who did not achieve glycemic control with oral combination therapy, the addition of exenatide or insulin glargine to the treatment regimen resulted in similar improvement in glycemic control (~1% reduction in hemoglobin A1c levels). Patients receiving exenatide experienced progressive weight reduction, as well as a greater likelihood of gastrointestinal adverse events.