Despite the initial encouraging results from trials that were conducted during the last 20 years, ARIs have not been established for the treatment of diabetic neuropathy yet. The main reasons for this are inconsistent results in subsequent trials and the unacceptable high rate of side-effects associated with the initially tested compounds. The lack of well-defined end points and the conduction of numerous small trials, instead of focussing on the most promising agents and conducting large pivotal trials is one of the reasons that are related to this outcome. In addition, the inability to produce an inhibitor that achieves satisfactory tissue penetration and enzyme inhibition, whereas at the same time is devoid of serious side-effects have also played a significant role. Currently, it seems that the interest in ARIs is significantly reduced and is doubtful if new ARIs will be tested clinically in the near future.
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