A METAANALYSIS OF TRIALS ON ALDOSE REDUCTASE INHIBITORS IN DIABETIC PERIPHERAL NEUROPATHY

Peripheral neuropathy is one of the most common and disabling long-ter m sequelae of diabetes mellitus. Aldose reductase inhibitors (ARIs) ha ve been proposed and are increasingly used in many countries for the p revention and treatment of diabetic neuropathy. The aim of this study was to review existing evidence on the effectiveness of ARIs in the tr eatment of peripheral diabetic neuropathy, with particular reference t o the type and clinical relevance of the end point used and to the con sistency of results across studies. Thirteen randomized clinical trial s (RTCs) comparing ARIs with placebo, published between 1981 and 1993 were included in the meta-analysis. Nerve conduction velocity (NCV) wa s the only end point reported in all trials. Treatment effect was thus evaluated in terms of NCV mean difference in four different nerves: m edian motor, median sensory, peroneal motor, and sural sensory. A stat istically significant reduction in decline of median motor NCV was pre sent in the treated group as compared to the control group (mean 0.91 ms(-1); 95% CI 0.41-1.42 ms(-1)). For peroneal motor, median sensory, and sural sensory nerves results did not show any clear benefit for pa tients treated with ARIs. When the analysis was limited to trials with at least 1-year treatment duration, a significant effect was present for peroneal motor NCV (mean 1.24 ms(-1); 95% CI 0.32-2.15 ms(-1)) and a benefit of borderline statistical significance was also present for median motor NCV (mean 0.69 ms(-1); 95% CI -0.07-1.45 ms(-1)). A hete rogeneous picture emerged when looking at the results of different stu dies and serious inconsistencies were also present in the direction of treatment effects among nerves in the same studies. Although the resu lts of 1-year treatment on motor NCV seem encouraging, the uncertainty about the reliability of the end-point employed and the short treatme nt duration do not allow any clear conclusion about the efficacy of AR Is in the treatment of peripheral diabetic neuropathy.