What is Epalrestat (Aldose reductase inhibitor)?

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Last updated: May 29, 2025 • View editorial policy

From the Guidelines

Epalrestat is a recommended treatment for diabetic neuropathy, particularly in Japan and some Asian countries, due to its ability to inhibit the aldose reductase enzyme and prevent nerve damage. The standard dosage of epalrestat is 150 mg daily, typically divided into three 50 mg doses taken with meals 1, 2. Epalrestat works by inhibiting the enzyme aldose reductase, which prevents excessive conversion of glucose to sorbitol in nerve cells during hyperglycemia. Accumulation of sorbitol leads to osmotic stress and cellular damage in diabetic patients, contributing to neuropathy symptoms. By blocking this pathway, epalrestat helps reduce nerve damage and may improve symptoms like numbness, tingling, and pain in extremities.

Some key points to consider when prescribing epalrestat include:

  • The importance of maintaining good glycemic control alongside epalrestat therapy, as the medication complements but doesn't replace proper diabetes management 1.
  • Regular monitoring of liver function is recommended during treatment, due to the potential for liver enzyme elevations 2.
  • Common side effects include gastrointestinal disturbances and skin reactions, which should be closely monitored 1, 2.
  • Treatment is usually long-term, as benefits typically develop over months of consistent use 1, 2.

It's worth noting that while ranirestat, another aldose reductase inhibitor, has shown strong efficacy in polyol pathway inhibition, with improvements in nerve function and clinical features of diabetic sensorimotor polyneuropathy after 60 weeks of therapy 2, epalrestat is the specific medication in question. Epalrestat's ability to reduce nerve damage and improve symptoms makes it a valuable treatment option for patients with diabetic neuropathy, and its use should be considered in conjunction with proper diabetes management and regular monitoring of potential side effects.

From the Research

Epalrestat Overview

  • Epalrestat is an aldose reductase inhibitor used for the treatment of diabetic neuropathy 3, 4, 5, 6.
  • It is approved in Japan for improving subjective neuropathy symptoms, abnormality of vibration sense, and abnormal changes in heartbeat associated with diabetic peripheral neuropathy 3.

Mechanism of Action

  • Epalrestat reduces sorbitol accumulation in the sciatic nerve, erythrocytes, and ocular tissues in animals, and in erythrocytes in humans 3.
  • By inhibiting aldose reductase, epalrestat may affect or delay the progression of the underlying disease process of diabetic neuropathy 3, 4.

Clinical Efficacy

  • Epalrestat has been shown to improve motor and sensory nerve conduction velocity and subjective neuropathy symptoms in clinical trials 3, 4, 5, 6.
  • Long-term treatment with epalrestat can delay the progression of diabetic neuropathy and ameliorate associated symptoms, particularly in subjects with good glycemic control and limited microangiopathy 4.
  • Epalrestat has been found to be effective in relieving subjective symptoms such as spontaneous pain, numbness, and hypoesthesia in patients with non-insulin-dependent diabetes mellitus 5, 6.

Safety and Tolerability

  • Epalrestat is well tolerated, with the most frequently reported adverse effects including elevations in liver enzyme levels and gastrointestinal-related events such as nausea and vomiting 3.
  • Epalrestat does not have adverse effects on glucose or lipid metabolism during treatment 5.

Comparison with Other Treatments

  • Epalrestat may serve as a new therapeutic option to prevent or slow the progression of diabetic neuropathy, unlike current treatment options that only provide symptomatic relief 3.
  • Other treatment options for painful diabetic neuropathy include gabapentinoids, duloxetine, tapentadol, and 8% capsaicin patch, as well as dorsal column spinal cord stimulation (SCS) for refractory cases 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.