Abstract

Background Aldose reductase inhibitors (ARIs) are potential disease modifiers for diabetes complications. We aimed to determine whether ranirestat, an ARI, could slow or reverse the course of diabetic sensorimotor polyneuropathy (DSP).

Methods 549 patients with DSP were randomized to treatment with placebo or ranirestat 10, 20, or 40 mg/d for 52 weeks in this multicenter, double-blind study. Efficacy was evaluated by nerve conduction studies (NCS), the modified Toronto Clinical Neuropathy Score (mTCNS), and quantitative sensory tests (QST).

Results At Week 52, the summed sensory (bilateral sural plus proximal median sensory) nerve conduction velocity (NCV) did not show significant changes from baseline (placebo 2.0 m/s compared to ranirestat 3.2-3.8 m/s). Significant improvement in the summed motor (peroneal, tibial, and median) NCV was observed with ranirestat 20 and 40 mg/d treatment at Week 12 (p ≤ 0.05), and at Week 24 and 36, and in the peroneal motor NCV at Weeks 36 and 52 (p ≤ 0.05) for the ranirestat 20 mg/d group. The mTCNS and QST did not differ between groups during the study. Ranirestat was well tolerated with no pertinent differences in drug-related adverse events, or effects on clinical laboratory parameters, vital signs, or ECGs between the four groups.

Conclusions Treatment with ranirestat appears to have an effect on motor nerve function in mild to moderate DSP, but the results of this study failed to show a statistically significant difference in sensory nerve function relative to placebo.