Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparative Aldose Reductase Inhibitor-Diabetes Complications Trial.
OBJECTIVE
We sought to evaluate the long-term efficacy and safety of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy.


METHODS
Subjects with diabetic neuropathy, median motor nerve conduction velocity (MNCV) >or=40 m/s, and HbA(1c) <or=9% were enrolled in this open-label, multicenter study and randomized to 150 mg/day epalrestat or a control group. After excluding the withdrawals, 289 (epalrestat group) and 305 (control group) patients were included in the analyses. The primary end point was change from baseline in median MNCV at 3 years. Secondary end points included assessment of other somatic nerve function parameters (minimum F-wave latency [MFWL] of the median motor nerve and vibration perception threshold [VPT]), cardiovascular autonomic nerve function, and subjective symptoms.


RESULTS
Over the 3-year period, epalrestat prevented the deterioration of median MNCV, MFWL, and VPT seen in the control group. The between-group difference in change from baseline in median MNCV was 1.6 m/s (P < 0.001). Although a benefit with epalrestat was observed in cardiovascular autonomic nerve function variables, this did not reach statistical significance compared with the control group. Numbness of limbs, sensory abnormality, and cramping improved significantly with epalrestat versus the control group. The effects of epalrestat on median MNCV were most evident in subjects with better glycemic control and with no or mild microangiopathies.


CONCLUSIONS
Long-term treatment with epalrestat is well tolerated and can effectively delay the progression of diabetic neuropathy and ameliorate the associated symptoms of the disease, particularly in subjects with good glycemic control and limited microangiopathy.
Hotta
Nigishi
N
Chubu Rosai Hospital, 1-10-6 Komei, Nagoya 455-8530, Japan. hotta@chubuh.rofuku.go.jp
Akanuma
Yasuo
Y
Kawamori
Ryuzo
R
Matsuoka
Kempei
K
Oka
Yoshitomo
Y
Shichiri
Motoaki
M
Toyota
Takayoshi
T
Nakashima
Mitsuyoshi
M
Yoshimura
Isao
I
Sakamoto
Nobuo
N
Shigeta
Yukio
Y
D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D001786:Blood Glucose / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology; D012236:Rhodanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D053778:Thiazolidines
D000449:Aldehyde Reductase; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D012236:Rhodanine; D053778:Thiazolidines; C038131:epalrestat