Epalrestat is a
carboxylic acid derivative which inhibits
aldose reductase, an
enzyme of the
sorbitol (
polyol) pathway. Under hyperglycaemic conditions
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, hyperaesthesia, coldness in the extremities,
muscular weakness,
dizziness, and orthostatic
fainting were also improved. Similar benefits were seen in a comparison with historical controls.
Epalrestat 300 mg/day for 1 or 3 years was also significantly superior to placebo or no treatment in improving electroretinogram parameters and photo stress recovery time in patients with
diabetic retinopathy. Improvements were also documented by funduscopy and
fluorescein angiography.
Epalrestat appeared most effective in patients with less severe
diabetes mellitus and more recent development of late-onset complications.
Epalrestat is apparently well tolerated with predominantly minor adverse events reported in clinical trials. Liver
enzyme elevations were most commonly reported but generally resolved spontaneously on
dose reduction or discontinuation. The effects of age and renal impairment on the efficacy and tolerability of
epalrestat require clarification, and data on its use in other late-onset complications of diabetes such as nephropathy are also lacking. Comparisons with other
aldose reductase inhibitors are also required to fully determine the role of
epalrestat. The suggested ability of
epalrestat to prevent the onset of
diabetic complications should also be investigated. Thus, available data suggest
epalrestat produces some improvement in the late-onset neuropathy and retinopathy associated with
diabetes mellitus, although additional trials are required to determine whether ongoing
therapy is necessary to maintain the improvements achieved and to confirm tolerability in the long term. Nevertheless, preliminary results suggest that
epalrestat may be a useful
drug in an area where there is a need for effective
therapy.