title: 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.
abstract: 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.
authors.affiliation: Chubu Rosai Hospital, 1-10-6 Komei, Nagoya 455-8530, Japan. hotta@chubuh.rofuku.go.jp
authors.forename: Nigishi
authors.initials: N
authors.lastname: Hotta
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Akanuma
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Kempei
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
authors.forename: Motoaki
authors.initials: M
authors.lastname: Shichiri
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Toyota
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Nakashima
authors.forename: Isao
authors.initials: I
authors.lastname: Yoshimura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Yukio
authors.initials: Y
authors.lastname: Shigeta
mesh_terms: 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
chemical_list: D000449:Aldehyde Reductase; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D012236:Rhodanine; D053778:Thiazolidines; C038131:epalrestat