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

• Published in: Journal of diabetes and its complications Vol. 29; no. 8; pp. 1287 - 1294
• Main Authors: Jaiswal, Mamta, Martin, Catherine L., Brown, Morton B., Callaghan, Brian, Albers, James W., Feldman, Eva L., Pop-Busui, Rodica
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2015; Elsevier Limited
• Subjects: Aged; Cardiac arrhythmia; Cardiovascular autonomic neuropathy; Clinical trial; Cohort Studies; Colleges & universities; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetic Neuropathies - epidemiology; Diabetic Neuropathies - physiopathology; Diabetic Neuropathies - prevention & control; Diabetic neuropathy; Diabetic peripheral neuropathy; Endocrinology & Metabolism; Exenatide; Female; Glargine; GLP-1receptor agonist; Glucagon-Like Peptide-1 Receptor - agonists; Glucagon-Like Peptide-1 Receptor - metabolism; Glycated Hemoglobin A - analysis; Heart rate; Humans; Hyperglycemia; Hyperglycemia - prevention & control; Hypoglycemia; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Incretins - adverse effects; Incretins - therapeutic use; Infections; Insulin; Insulin Glargine - adverse effects; Insulin Glargine - therapeutic use; Male; Michigan - epidemiology; Middle Aged; Nausea; Neural Conduction - drug effects; Peptides - adverse effects; Peptides - therapeutic use; Pilot Projects; Prevalence; Quality of Life; Severity of Illness Index; Venoms - adverse effects; Venoms - therapeutic use; Clinical trial; GLP-1receptor agonist; Diabetic peripheral neuropathy; Exenatide; Cardiovascular autonomic neuropathy; Glargine
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2015.07.013

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). 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. 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. 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.