Exenatide is a glucagon-like peptide-1 (GLP-1) agonist. The GLP-1 is principally produced in the enteroendocrine cells of the ileum in response to local contact with postprandial nutrients in the intestinal lumen.1 It stimulates insulin secretion and inhibits glucagon release. Long-acting GLP-1 receptor agonists were developed as glucose-lowering drugs for the treatment of type 2 diabetes mellitus. In the large phase 3 trials conducted for diabetes, it was observed that these drugs also produced weight loss. The effect of GLP-1 agonists on body weight is believed to be a central effect leading to reduced food intake.2 Collectively, the studies in obese adults with or without diabetes demonstrate that long-acting GLP-1 agonists promote weight loss on the order of 2% to 4%.3 In this issue of the journal, Kelly et al4 report the results of a randomized, double-blind, placebo-controlled clinical trial of exenatide vs placebo injected twice daily for 3 months in severely obese adolescents.