Stratified analyses for selecting appropriate target patients with diabetic peripheral neuropathy for long-term treatment with an aldose reductase inhibitor, epalrestat.
OBJECTIVE
The long-term efficacy of epalrestat, an aldose reductase inhibitor, in improving subjective symptoms and nerve function was comprehensively assessed to identify patients with diabetic peripheral neuropathy who responded to epalrestat treatment.


METHODS
Stratified analyses were conducted on data from patients in the Aldose Reductase Inhibitor-Diabetes Complications Trial (ADCT). The ADCT included patients with diabetic peripheral neuropathy, median motor nerve conduction velocity > or = 40 m/s and with glycated haemoglobin (HbA(1c)) < or = 9.0%. Longitudinal data on HbA(1c) and subjective symptoms of the patients for 3 years were analysed (epalrestat n = 231, control subjects n = 273). Stratified analyses based on background variables (glycaemic control, grades of retinopathy or proteinuria) were performed to examine the relationship between subjective symptoms and nerve function. Multiple logistic regression analyses were conducted.


RESULTS
Stratified subgroup analyses revealed significantly better efficacy of epalrestat in patients with good glycaemic control and less severe diabetic complications. In the control group, no improvement in nerve function was seen regardless of whether symptomatic benefit was obtained. In the epalrestat group, nerve function deteriorated less or improved in patients whose symptoms improved. The odds ratio of the efficacy of epalrestat vs. control subjects was approximately 2 : 1 (4 : 1 in patients with HbA(1c) < or = 7.0%).


CONCLUSIONS
Our results suggest that epalrestat, an aldose reductase inhibitor, will provide a clinically significant means of preventing and treating diabetic neuropathy if used in appropriate patients.
Hotta
N
N
Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan. hotta@chubuh.rofuku.go.jp
Kawamori
R
R
Atsumi
Y
Y
Baba
M
M
Kishikawa
H
H
Nakamura
J
J
Oikawa
S
S
Yamada
N
N
Yasuda
H
H
Shigeta
Y
Y
D000284:Administration, Oral; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D003930:Diabetic Retinopathy / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011507:Proteinuria / Q000209:etiology; D012236:Rhodanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D053778:Thiazolidines / Q000008:administration & dosage*; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D012236:Rhodanine; D053778:Thiazolidines; C038131:epalrestat