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.
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).


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.
Department of Neurology, University of Michigan, Ann Arbor, MI.
Mamta
M
Jaiswal
Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
Catherine L
CL
Martin
Department of Biostatistics, University of Michigan, Ann Arbor, MI.
Morton B
MB
Brown
Department of Neurology, University of Michigan, Ann Arbor, MI.
Brian
B
Callaghan
Department of Neurology, University of Michigan, Ann Arbor, MI.
James W
JW
Albers
Department of Neurology, University of Michigan, Ann Arbor, MI.
Eva L
EL
Feldman
Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI. Electronic address: rpbusui@med.umich.edu.
Rodica
R
Pop-Busui
D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D000077270:Exenatide; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D054795:Incretins / Q000009:adverse effects / Q000627:therapeutic use*; D000069036:Insulin Glargine / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D015995:Prevalence; D011788:Quality of Life; D012720:Severity of Illness Index; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D000069036:Insulin Glargine; D010455:Peptides; D014688:Venoms; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human
Cardiovascular autonomic neuropathy; Clinical trial; Diabetic peripheral neuropathy; Exenatide; GLP-1receptor agonist; Glargine