A Cochrane review 1 (abstract , review ) included 29 trials assessing the primary outcome, change in neurological function with aldose reductase inhibitors (either sorbinil, tolrestat, ponalrestat, zopolrestat, zenarestat, epalrestat, ranirestat, or fidarestat). Sufficient data for meta-analysis were only available in 13 studies (n=1,788). There was no overall significant difference between the treated and control groups (SMD –0.25, 95% CI –0.56 to 0.05), although one subgroup analysis (four trials using tolrestat) favored treatment. A benefit for neuropathic symptoms was suggested by a group of trials using a dichotomized endpoint (improvement or not), but this was contradicted by another group of trials which measured symptoms on a continuous scale. There was no overall benefit on nerve conduction parameters (27 studies) or foot ulceration (one study). Quality of life was not assessed in any of the studies. While most adverse events were infrequent and minor, three compounds had dose limiting adverse events that lead to their withdrawal from human use: severe hypersensitivity reactions with sorbinil, elevation of creatinine with zenarestat, and alteration of liver function with tolrestat.
Comment: The quality of evidence is downgraded by limitations in study quality, by inconsistency (heterogeneity in interventions and outcomes) and by potential reporting bias.
1. Chalk C, Benstead TJ, Moore F. Aldose reductase inhibitors for the treatment of diabetic polyneuropathy. Cochrane Database Syst Rev 2007 Oct 17;(4):CD004572. [PMID:17943821]
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