Diabetes Care, Vol 19, Issue 10 1091-1096, Copyright © 1996 by American Diabetes Association

ARTICLES

The efficacy of tolrestat in the treatment of diabetic peripheral neuropathy. A meta-analysis of individual patient data

A Nicolucci, F Carinci, JG Graepel, TC Hohman, F Ferris and JM Lachin
Department of Clinical Pharmacology and Epidemiology-Istituto di Ricerche Farmacologiche Mario Negri, S. Maria Imbaro (CH), Itlay. nicolucci@cmns.mnegri.it

OBJECTIVE: The aim of this meta-analysis was to review the existent evidence on the effectiveness of tolrestat in the treatment of diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS: Individual patient data on 738 subjects from the three randomized clinical trials published on this topic were analyzed using changes in motor nerve conduction velocities (NCVs) as endpoints. Nerves investigated included median, ulnar, tibial, and peroneal. RESULTS: The pooled analysis of NCV taken as a continuous measurement showed a significant treatment effect, the magnitude of this benefit being approximately equal to 1 m/s for all the nerves investigated. When looking at the proportion of patients experiencing a loss of NCV of at least 1 or 2 m/s in at least two out of the four nerves investigated, it emerged that treatment reduced by > 40% the risk of such outcomes after adjusting for patients' characteristics. The odds ratios relative to the placebo group were 1.82 (1.30-2.52) and 1.70 (1.15-2.48) for a decrease of 1 and 2 m/s, that is, placebo-treated patients have an 82 and 70% increased risk for a loss of nerve function of 1 and 2 m/s, respectively. No statistically significant difference in treatment effect emerged after stratification according to baseline motor NCV and glycated hemoglobin levels. CONCLUSIONS: After a treatment duration ranging between 24-52 weeks, patients treated with tolrestat had a reduced risk for developing nerve function loss compared with placebo-treated patients. Future long-term trials are needed to evaluate the impact of the treatment on more clinically meaningful endpoints such as the development of foot complications.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Ziegler Polyneuropathy in the diabetic patient--update on pathogenesis and management Nephrol. Dial. Transplant., September 1, 2004; 19(9): 2170 - 2175. [Full Text] [PDF]

				N. E Cameron The aetiology of neuropathy in experimental diabetes The British Journal of Diabetes & Vascular Disease, March 1, 2003; 3(2): 98 - 105. [Abstract] [PDF]

				C. Yabe-Nishimura Aldose Reductase in Glucose Toxicity: A Potential Target for the Prevention of Diabetic Complications Pharmacol. Rev., March 1, 1998; 50(1): 21 - 34. [Abstract] [Full Text] [PDF]

				A. E Heesom, A. Millward, and A. G Demaine Susceptibility to diabetic neuropathy in patients with insulin dependent diabetes mellitus is associated with a polymorphism at the 5' end of the aldose reductase gene J. Neurol. Neurosurg. Psychiatry, February 1, 1998; 64(2): 213 - 216. [Abstract] [Full Text] [PDF]