Effects of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy and gastroparesis

Intern Med. 2003 Aug;42(8):655-64. doi: 10.2169/internalmedicine.42.655.


Objective: Diabetic patients with severe autonomic nervous disorder show delayed gastric emptying accompanied by diabetic gastroparesis, which decreases the electric activity of the stomach associated with gastric motility. It is reported that epalrestat, an aldose reductase inhibitor, is useful for treating diabetic neuropathy. Therefore, we evaluated whether this drug improves the decreased gastric motility in diabetic patients.

Methods: The present study evaluated the electrogastrograms (EGG) and autonomic nervous activity in 15 healthy volunteers (N group), and in 15 diabetic patients before and after the administration of epalrestat (DM group). Autonomic nervous activity was evaluated by spectral analysis of heart rate variability. The EGGs were recorded before and after oral administration of epalrestat (3 months or more) in the DM group.

Results: The dominant frequency of EGG was 3 cycles/min (cpm) in the N group. However, these 3 cpm waves disappeared with bradygastria, and postprandial increases in the peak powers of EGG were not observed in the DM group. Both the amplitude of 3 cpm waves and the postprandial peak powers were significantly increased after the administration of epalrestat. The parameters of autonomic nervous activities (LF power, HF power, and the LF/HF ratio) were significantly lower in the DM group before the administration of epalrestat than in the N group. However, these parameters were improved after the administration of epalrestat.

Conclusion: Since gastroparesis is a form of diabetic dysautonomia, complication by gastroparesis may influence blood sugar control and the absorbance of oral antidiabetics. Epalrestat significantly increased the amplitude of 3 cpm waves on EGG and improved the spectral analytical parameters of heart rate variability. These findings suggest that epalrestat is useful for the treatment of diabetic gastroparesis.

MeSH terms

  • Aged
  • Aldehyde Reductase / antagonists & inhibitors*
  • Autonomic Nervous System / drug effects
  • Diabetic Neuropathies / diagnosis
  • Diabetic Neuropathies / drug therapy*
  • Electrodiagnosis / methods
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Gastrointestinal Motility / drug effects
  • Gastroparesis / diagnosis
  • Gastroparesis / drug therapy*
  • Glycated Hemoglobin A / drug effects
  • Heart Rate / drug effects
  • Humans
  • Male
  • Middle Aged
  • Rhodanine / analogs & derivatives*
  • Rhodanine / pharmacology
  • Rhodanine / therapeutic use*
  • Thiazolidines


  • Enzyme Inhibitors
  • Glycated Hemoglobin A
  • Thiazolidines
  • epalrestat
  • Rhodanine
  • Aldehyde Reductase