Effects of exenatide on measures of diabetic neuropathy in subjects with type 2 diabetes: results from an 18-month proof-of-concept open-label randomized study

ObjectiveExperimental studies have reported potential benefit of glucagon-like peptide-1(GLP-1) receptor agonists in preventing diabetic peripheral neuropathy (DPN). We therefore performed a proof-of-concept pilot study to evaluate the effect of exenatide, a GLP-1 agonist, on measures of DPN and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes (T2D).Research Design and MethodsForty-six T2D subjects (age 54 ± 10 years, diabetes duration 8 ± 5 years, HbA1c 8.2 ± 1.3%) with mild to moderate DPN at baseline were randomized to receive either twice daily exenatide (n = 22) or daily insulin glargine (n = 24). The subjects, with similar HbA1c levels, were followed for 18 months. The primary end point was the prevalence of confirmed clinical neuropathy (CCN). Changes in measures of CAN, other measures of small fiber neuropathy such as intra-epidermal nerve fiber density (IENFD), and quality of life were also analyzed.ResultsGlucose control was similar in both groups during the study. There were no statistically significant treatment group differences in the prevalence of CCN, IENFD, measures of CAN, nerve conductions studies, or quality of life indices.ConclusionsIn this pilot study of patients with T2D and mild to moderate DPN, 18 months of exenatide treatment had no significant effect on measures of neuropathy compared with glargine treatment.