The efficacy of tolrestat in the treatment of diabetic peripheral neuropathy. A meta-analysis of individual patient data.
OBJECTIVE
The aim of this meta-analysis was to review the existent evidence on the effectiveness of tolrestat in the treatment of diabetic peripheral neuropathy.


METHODS
Individual patient data on 738 subjects from the three randomized clinical trials published on this topic were analyzed using changes in motor nerve conduction velocities (NCVs) as endpoints. Nerves investigated included median, ulnar, tibial, and peroneal.


RESULTS
The pooled analysis of NCV taken as a continuous measurement showed a significant treatment effect, the magnitude of this benefit being approximately equal to 1 m/s for all the nerves investigated. When looking at the proportion of patients experiencing a loss of NCV of at least 1 or 2 m/s in at least two out of the four nerves investigated, it emerged that treatment reduced by > 40% the risk of such outcomes after adjusting for patients' characteristics. The odds ratios relative to the placebo group were 1.82 (1.30-2.52) and 1.70 (1.15-2.48) for a decrease of 1 and 2 m/s, that is, placebo-treated patients have an 82 and 70% increased risk for a loss of nerve function of 1 and 2 m/s, respectively. No statistically significant difference in treatment effect emerged after stratification according to baseline motor NCV and glycated hemoglobin levels.


CONCLUSIONS
After a treatment duration ranging between 24-52 weeks, patients treated with tolrestat had a reduced risk for developing nerve function loss compared with placebo-treated patients. Future long-term trials are needed to evaluate the impact of the treatment on more clinically meaningful endpoints such as the development of foot complications.
Nicolucci
A
A
Department of Clinical Pharmacology and Epidemiology-Istituto di Ricerche Farmacologiche Mario Negri, S. Maria Imbaro (CH), Itlay. nicolucci@cmns.mnegri.it
Carinci
F
F
Graepel
J G
JG
Hohman
T C
TC
Ferris
F
F
Lachin
J M
JM
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D009431:Neural Conduction; D010543:Peroneal Nerve / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D013979:Tibial Nerve / Q000503:physiopathology; D016896:Treatment Outcome; D014459:Ulnar Nerve / Q000503:physiopathology
D004791:Enzyme Inhibitors; D009281:Naphthalenes; C040550:tolrestat; D000449:Aldehyde Reductase