Previous in vitro studies have suggested that the diabetes drug exenatide — a glucagon-like peptide 1 receptor agonist — has neurotrophic and neuroprotective effects. This clinical study investigated the efficacy of exenatide in 45 patients with moderate Parkinson's disease. Exanatide given for 12 months improved motor symptoms (P = 0.037) and some cognitive measures, although weight loss was commonly observed. These data support larger double-blind trials of exenatide as a potential disease-modifying drug in Parkinson's disease.