Fidarestat (SNK-860), a potent aldose reductase inhibitor, normalizes the elevated sorbitol accumulation in erythrocytes of diabetic patients

Abstract

Sorbitol accumulation in nerves has been regarded as one of the major causes of diabetic neuropathy. In this study, fidarestat (SNK-860; 1 mg daily), a potent new aldose reductase inhibitor (ARI), or the commercially available ARI epalrestat (150 mg daily), was administered for 4 weeks to 58 Type 2 diabetic patients. Treatment with these drugs had no effect on glycemic control, judging from plasma glucose and HbA 1c levels. However, fidarestat treatment normalized the elevated sorbitol content of erythrocytes under fasting as well as postprandial conditions. In contrast, the effect of epalrestat was minimal. There were no major side effects with fidarestat. Thus, fidarestat is considered to be a potent and promising ARI, possibly useful for both preventing and treating diabetic neuropathy. Further studies are needed to clarify how much the occurrence and progression of diabetic neuropathy are inhibited by normalizing sorbitol elevation with fidarestat treatment.