Tolrestat for mild diabetic neuropathy

A 52-week, randomized, placebo-controlled trial

Dario Giugliano, Raffaele Marfella, Antonio Quatraro, Nicoletta De Rosa, Teresa Salvatore, Domenico Cozzolino, Antonio Ceriello, Roberto Torella

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Objective: To evaluate the effectiveness and safety of tolrestat, an aldose-reductase inhibitor, in patients with mild diabetic autonomic and peripheral neuropathy. Design: Randomized, placebo-controlled, double-blind 52-week trial. Setting: University hospital clinic. Patients: Forty-five diabetic patients with asymptomatic autonomic neuropathy identified by at least one pathologic cardiovascular reflex test result. Interventions: All patients were given placebo during a 4-week run-in period (single-blind). Twenty patients were randomly assigned to continue to receive placebo, and 25 were assigned to treatment with tolrestat (200 mg/d given in the morning). Measurements and Results: At 12 months, improvements in nerve functions occurred in patients receiving tolrestat. Compared with baseline values, postural hypotension decreased by a value of 5.9 mm Hg (95% Cl, 1.6 to 8.7); deep-breathing, maximum/minimum heart rate (expiration/inspiration ratio) increased by a value of 0.026 (Cl, 0.015 to 0.036); and lying-to-standing heart rate ratio (30:15 ratio) increased by a value of 0.032 (Cl, 0.027 to 0.052). In the placebo group, all test results except postural hypotension deteriorated. Vibration perception threshold at the malleolus and great toe of the dominant leg improved in the tolrestat group (- 1.4; Cl, - 3.69 to - 1.09) but tended to worsen in the placebo group during the study period. No important side effects were detected in either group. Conclusions: The progression of mild diabetic autonomic and peripheral neuropathy may be halted or even reversed by pharmacologic intervention with the aldose-reductase inhibitor tolrestat.

Original languageEnglish
Pages (from-to)7-11
Number of pages5
JournalAnnals of Internal Medicine
Volume118
Issue number1
Publication statusPublished - Jan 1 1993

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Diabetic Neuropathies
Randomized Controlled Trials
Placebos
Aldehyde Reductase
Orthostatic Hypotension
Peripheral Nervous System Diseases
Heart Rate
Hallux
Vibration
Reflex
tolrestat
Leg
Respiration
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Giugliano, D., Marfella, R., Quatraro, A., De Rosa, N., Salvatore, T., Cozzolino, D., ... Torella, R. (1993). Tolrestat for mild diabetic neuropathy: A 52-week, randomized, placebo-controlled trial. Annals of Internal Medicine, 118(1), 7-11.

Tolrestat for mild diabetic neuropathy : A 52-week, randomized, placebo-controlled trial. / Giugliano, Dario; Marfella, Raffaele; Quatraro, Antonio; De Rosa, Nicoletta; Salvatore, Teresa; Cozzolino, Domenico; Ceriello, Antonio; Torella, Roberto.

In: Annals of Internal Medicine, Vol. 118, No. 1, 01.01.1993, p. 7-11.

Research output: Contribution to journalArticle

Giugliano, D, Marfella, R, Quatraro, A, De Rosa, N, Salvatore, T, Cozzolino, D, Ceriello, A & Torella, R 1993, 'Tolrestat for mild diabetic neuropathy: A 52-week, randomized, placebo-controlled trial', Annals of Internal Medicine, vol. 118, no. 1, pp. 7-11.
Giugliano D, Marfella R, Quatraro A, De Rosa N, Salvatore T, Cozzolino D et al. Tolrestat for mild diabetic neuropathy: A 52-week, randomized, placebo-controlled trial. Annals of Internal Medicine. 1993 Jan 1;118(1):7-11.
Giugliano, Dario ; Marfella, Raffaele ; Quatraro, Antonio ; De Rosa, Nicoletta ; Salvatore, Teresa ; Cozzolino, Domenico ; Ceriello, Antonio ; Torella, Roberto. / Tolrestat for mild diabetic neuropathy : A 52-week, randomized, placebo-controlled trial. In: Annals of Internal Medicine. 1993 ; Vol. 118, No. 1. pp. 7-11.
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N2 - Objective: To evaluate the effectiveness and safety of tolrestat, an aldose-reductase inhibitor, in patients with mild diabetic autonomic and peripheral neuropathy. Design: Randomized, placebo-controlled, double-blind 52-week trial. Setting: University hospital clinic. Patients: Forty-five diabetic patients with asymptomatic autonomic neuropathy identified by at least one pathologic cardiovascular reflex test result. Interventions: All patients were given placebo during a 4-week run-in period (single-blind). Twenty patients were randomly assigned to continue to receive placebo, and 25 were assigned to treatment with tolrestat (200 mg/d given in the morning). Measurements and Results: At 12 months, improvements in nerve functions occurred in patients receiving tolrestat. Compared with baseline values, postural hypotension decreased by a value of 5.9 mm Hg (95% Cl, 1.6 to 8.7); deep-breathing, maximum/minimum heart rate (expiration/inspiration ratio) increased by a value of 0.026 (Cl, 0.015 to 0.036); and lying-to-standing heart rate ratio (30:15 ratio) increased by a value of 0.032 (Cl, 0.027 to 0.052). In the placebo group, all test results except postural hypotension deteriorated. Vibration perception threshold at the malleolus and great toe of the dominant leg improved in the tolrestat group (- 1.4; Cl, - 3.69 to - 1.09) but tended to worsen in the placebo group during the study period. No important side effects were detected in either group. Conclusions: The progression of mild diabetic autonomic and peripheral neuropathy may be halted or even reversed by pharmacologic intervention with the aldose-reductase inhibitor tolrestat.

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