THE EFFICACY OF TOLRESTAT IN THE TREATMENT OF DIABETIC PERIPHERAL NEUROPATHY - A METAANALYSIS OF INDIVIDUAL PATIENT DATA

OBJECTIVE - The aim of this meta-analysis was to review the existent e vidence on the effectiveness of tolrestat in the treatment of diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS - Individual patie nt data on 738 subjects from the three randomized clinical trials publ ished on this topic were analyzed using changes in motor nerve conduct ion velocities (NCVs) as endpoints, Nerves investigated included media n, ulnar, tibial, and peroneal, RESULTS - The pooled analysis of NCV t aken as a continuous measurement showed a significant treatment effect , the magnitude of this benefit being approximately equal to 1 mis for all the nerves investigated. When looking at the proportion of patien ts experiencing a loss of NCV of at least 1 or 2 mis in at least two o ut of the four nerves investigated, it emerged that treatment reduced by >40% the risk of such outcomes after adjusting for patients' charac teristics. 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 signi ficant difference in treatment effect emerged after stratification acc ording to baseline motor NCV and glycated hemoglobin levels. CONCLUSIO NS - After a treatment duration ranging between 24-52 weeks, patients treated with tolrestat had a reduced risk for developing nerve functio n 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.