Effects of an aldose reductase inhibitor, epalrestat, on diabetic neuropathy. Clinical benefit and indication for the drug assessed from the results of a placebo-controlled double-blind study

The clinical efficacy of epalrestat (150 mg/day, 50 mg tid, po; A group), an aldose reductase inhibitor, was evaluated in 196 patients with diabetic neuropathy by a double-blind study using placebo (9 mg/day, 3 mg tid, po; P group) as a control for 12 weeks. The disappearance rates of upper limb spontaneous pain were 42.9% and 12.0% in the A and P groups, respectively, and those of lower limb spontaneous pain 48.6% and 22.6%, thus being significantly higher in the A group (p< 0.05, logrank-test). The motor nerve conduction velocity of the peroneal nerve significantly increased only in the A group (Δ 1.6 ± 0.6 m/sec, p< 0.01, paired t-test), and the extent of increase in that of the median nerve was significantly greater in the A group than in the P group (p< 0.05). Thresholds of vibratory sensation and autonomic nerve function were also significantly improved in the A group (p< 0.05). The data were reanalyzed by dividing patients into two groups according to their HbA1c. values. The improvement ratings of subjective symptoms and of nerve function tests for cases with HbA1c. 7.5% were both significantly different between the A and P groups, with the improvement rate being higher in the A group, and also higher as compared to the analysis for cases with HbA1c< 7.5%. This reanalysis also revealed that the effects of epalrestat were marked in patients receiving the drug as early after the onset of diabetic neuropathy as possible (3 yrs ) and were more marked in patients with mild or moderate neuropathy than in those with severe neuropathy. Our findings suggest that epalrestat is a highly effective agent for the treatment of diabetic neuropathy