Abstract
It has been more than 30 years since the first aldose reductase inhibitor (ARI) was tested in diabetic and galactosemic rats and found to control the polyol accumulation. Since then, a considerable number of ARIs have been tested in experimental and human diabetes. Despite the initial encouraging results from tests that were conducted for the past 20 years, ARIs have not been established for the treatment of diabetic neuropathy yet. The main reasons for this are inconsistent results and the unacceptable high rate of side-effects associated with the initially tested compounds. The lack of well-defined end points and the inability to produce an inhibitor that achieves satisfactory tissue penetration and enzyme inhibition are other major contributing factors for this failure. This chapter focuses on the clinical trials that have examined the effect of all tested ARIs on human diabetic neuropathy.
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