8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Aldose reductase inhibitors: the end of an era or the need for different trial designs?

      Diabetes
      Aldehyde Reductase, antagonists & inhibitors, Autonomic Nervous System, physiopathology, Diabetic Neuropathies, drug therapy, Enzyme Inhibitors, therapeutic use, Humans, Imidazoles, pharmacokinetics, Imidazolidines, Isoquinolines, Naphthalenes, Phthalazines, Time Factors

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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 rigorous quality control to definitively confirm the utility of ARIs in the treatment of diabetic distal symmetrical polyneuropathy and autonomic neuropathy.

          Related collections

          Author and article information

          Comments

          Comment on this article