What is the role of aldose reductase inhibitors in the treatment of diabetic neuropathy?

Updated: Jan 17, 2020
  • Author: Dianna Quan, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Aldose reductase inhibitors block the rate-limiting enzyme in the polyol pathway that is activated in hyperglycemic states. Numerous studies of aldose reductase inhibitors (eg, alrestatin, sorbinil, tolrestat, epralrestat) have been published in the past 30 years, but many of the earlier trials had problems related to poor study design (eg, enrolling patients with advanced neuropathy who were unlikely to benefit from treatment).

These medications are not currently available in the United States. [88, 89] Epralrestat is currently marketed only in Japan. Epalrestat reduces intracellular sorbitol accumulation, which has been implicated in the pathogenesis of late-onset complications of diabetes mellitus. Epalrestat 150 mg/day for 12 weeks improved motor and sensory nerve conduction velocity and vibration threshold compared with baseline and placebo in patients with diabetic neuropathy. Subjective symptoms, including pain, numbness, hyperesthesia, coldness in the extremities, muscular weakness, dizziness, and orthostatic fainting, were also improved. [90, 91]

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