Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence
OBJECTIVE Experimental 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 METHODS Forty-six T2D subjects (age 54±10years, diabetes duration 8±5years, 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 18months. 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. RESULTS Glucose 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. CONCLUSIONS In this pilot study of patients with T2D and mild to moderate DPN, 18months of exenatide treatment had no significant effect on measures of neuropathy compared with glargine treatment.