Research article summary (published 29 Jun 1993):

Withdrawal of the aldose reductase inhibitor tolrestat in patients with diabetic neuropathy: effect on nerve function. The Tolrestat Study Group.

Full Abstract

A double-blind, placebo-controlled clinical trial was conducted to study the effects of discontinuing tolrestat, an aldose reductase inhibitor, on peripheral sensorimotor diabetic neuropathy. After an average of 4.2 years of continuous tolrestat use, 372 patients were randomly assigned to either placebo or continued tolrestat therapy and were followed for 52 weeks. After 3 months, patients who perceived worsening of symptoms of neuropathy were allowed to switch once to the alternate treatment group while maintaining the double-blind. Patients assigned to placebo had significant deterioration in motor nerve conduction velocity (MNCV) while those maintained on tolrestat did not (p < 0.05). The 28 patients who were randomly assigned to tolrestat and elected to switch to placebo had a significant deterioration in MNCV while the 36 assigned to placebo who switched to tolrestat had a significant improvement (p < 0.05). Treatment differences in favor of tolrestat were observed for sensation in the toes as well as for pain (p < 0.05). These data indicate that withdrawal from long-term treatment with tolrestat has a detrimental effect on several measures of diabetic neuropathy, whereas continuation of treatment is associated with stabilization of these measures, suggesting a continued role for polyol pathway activity in late neuropathy.

Author information

Author/s: Santiago, J V (JV); Snksen, P H (PH); Boulton, A J (AJ); Macleod, A (A); Beg, M (M); Bochenek, W (W); Graepel, G J (GJ); Gonen, B (B);

Affiliation: Diabetes Research and Training Center, Washington University School of Medicine, St. Louis, Missouri.

Journal and publication information

Publication Type: Clinical Trial; Journal Article; Randomized Controlled Trial

Journal: Journal of diabetes and its complications (J Diabetes Complications), published in UNITED STATES. (Language: eng)

Reference: -1993 Jul-Sep; vol 7 (issue 3) : pp 170-8

Dates: Created 1993/09/09; Completed 1993/09/09; Revised 2004/11/17;

PMID: 8343611, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Aldehyde Reductase - antagonists & inhibitors Blood Glucose - metabolism Diabetes Mellitus, Type 1 - blood; physiopathology Diabetes Mellitus, Type 2 - blood; physiopathology Diabetic Neuropathies - blood; drug therapy; physiopathology Double-Blind Method Female Hemoglobin A, Glycosylated - analysis Humans Male

Male Median Nerve - physiopathology Middle Aged Naphthalenes - therapeutic use Neural Conduction Pain - physiopathology Peripheral Nerves - physiopathology Placebos Sural Nerve - physiopathology Ulnar Nerve - physiopathology

Associated Chemicals: Blood Glucose (0) ; Hemoglobin A, Glycosylated (0) ; Naphthalenes (0) ; Placebos (0) ; tolrestat (82964-04-3) ; Aldehyde Reductase (EC 1.1.1.21)

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