Epalrestat: An Aldose Reductase Inhibitor for the Treatment of Diabetic Neuropathy

Mary Ann Ramirez, PharmD; Nancy L. Borja, PharmD


Pharmacotherapy. 2008;28(5):646-655. 

In This Article


Epalrestat is currently the only aldose reductase inhibitor approved to treat subjective and objective symptoms of diabetic neuropathy; however, it is approved only in Japan. The safety and efficacy of epalrestat have not yet been established internationally. Data suggest that epalrestat is well tolerated in Japanese patients and improves subjective neuropathy symptoms, nerve conduction velocity, and other nerve function tests in patients with mild-to-moderate diabetic neuropathy. The aldose reductase inhibitors have a distinct mechanism of action, affecting the underlying disease process in diabetic neuropathy, although the extent of the polyol pathway involvement is yet to be determined. Studies are necessary to determine the outcome of disease progression, renal and hepatic insufficiency, and age on the effectiveness of therapy. Factors that could affect the optimal dosage of epalrestat include genetic polymorphisms and variability in the expression of aldose reductase, but studies are needed to determine their influence. Changes in nerve conduction velocity do not always correlate with subjective symptoms; therefore, the optimal time to start epalrestat is unknown. Epalrestat may serve as a new therapeutic option to prevent or slow the progression of diabetic neuropathy. Future long-term, comparative studies in diverse patient populations are needed for clinical application.