Aldose reductase inhibitors: The end of an era or the need for different trial designs?
Aldose reductase inhibitors: The end of an era or the need for different trial designs?
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DOI：
10.2337/diab.46.2.s82
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发表时间：
1997-09-01
期刊：
影响因子：
7.7
通讯作者：
Gelber, DA
中科院分区：
文献类型：
--
作者：
Pfeifer, MA;Schumer, MP;Gelber, DA
尽管16年来进行了多次尝试，但用于治疗糖尿病神经病变的醛糖还原酶抑制剂（ARI）试验的结果尚未证明有效性。本文回顾了ARI的每一项试验，分析了混杂因素，并提出了未来的研究方向。考虑的混杂因素包括药代动力学（ARI对人体神经的渗透）、试验时长（就糖尿病神经病变的自然史而言）、试验终点（可逆性或进展减缓）、临床测量的重现性（就把握度计算而言）、终点的标准化和质量控制以及终点中有临床意义的差异。我们的结论是，阿里斯在糖尿病远端对称性多发性神经病变和自主神经病变的治疗中最有可能产生有益的效果，但阿里斯的临床作用是减缓糖尿病神经病变的进展，而不是逆转它。未来的试验设计应具有足够的统计功效，并考虑终点测量值在足够长的时间内的变异性，并进行严格的质量控制，以明确证实阿里斯在治疗糖尿病远端对称性多发性神经病和自主神经病中的效用。
Despite numerous attempts over 16 years, the results of aldose reductase inhibitor (ARI) trials for the treatment of diabetic neuropathy have not proven efficacy. this paper reviews each of the ARI trials, examines confounding factors, and proposes a future course. The confounding factors considered are pharmacokinetics (ARI penetration of human nerve), length of trial (in terms of the natural history of diabetic neuropathy), trial endpoints (reversibility or slowing of progression), reproducibility of clinical measurements (in terms of power calculations), standardization and quality control of endpoints, and clinically meaningful differences in endpoints. We conclude that ARIs are most likely to have a beneficial effect in the management of diabetic distal symmetrical polyneuropathy and autonomic neuropathy but that the clinical role of ARIs is to slow the progression of diabetic neuropathy rather than to reverse it. Future trials should be designed with adequate statistical power, with consideration of the variability of the endpoint measurements for long enough duration, and with rigourous quality control to definitively confirm the utility of ARIs in the treatment of diabetic distal symmetrical polyneuropathy and autonomic neuropathy.