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Meta-Analysis
. 2007 Oct 17;2007(4):CD004572.
doi: 10.1002/14651858.CD004572.pub2.

Aldose reductase inhibitors for the treatment of diabetic polyneuropathy

C Chalk  1 , T J Benstead, F Moore
Affiliations
Meta-Analysis

Aldose reductase inhibitors for the treatment of diabetic polyneuropathy

C Chalk et al. Cochrane Database Syst Rev. .

Abstract

Background: Polyneuropathy, a common complication of diabetes mellitus, causes pain and sensory and motor deficits in the limbs, and is also an important independent predictor of foot ulceration. Inhibiting the metabolism of glucose by the polyol pathway using aldose reductase inhibitors is a potential mechanism to slow or reverse the neuropathy's progression.

Objectives: To assess the effects of aldose reductase inhibitors on the progression of symptoms, signs or functional disability in diabetic polyneuropathy.

Search strategy: We searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (from January 1966 to May 2007), EMBASE (from January 1980 to May 2007) and LILACS (from 1982 to May 2007). We reviewed bibliographies of randomized trials identified, and contacted authors and experts in the field.

Selection criteria: We included randomized controlled trials comparing an aldose reductase inhibitor with control, and lasting at least six months. The primary outcome measure was change in neurological function, measured in various ways, including strength testing, sensory examination, and composite scores of neurological examination. Secondary outcome measures were nerve conduction studies, neuropathic symptoms, quality of life, occurrence of foot ulcers and adverse effects.

Data collection and analysis: Trials included in the review were selected and assessed independently by at least two of us. Methodological criteria and study results were recorded on data extraction forms.

Main results: Thirty-two randomized controlled trials meeting the inclusion criteria were identified. Many had significant methodological flaws. Change in neurological function, our primary outcome measure, was assessed in 29 trials, but sufficient data for meta-analysis were only available in 13 studies, involving 879 treated participants and 909 controls. 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.

Authors' conclusions: We found no statistically significant difference between aldose reductase inhibitors and placebo in the treatment of diabetic polyneuropathy. Any future clinical trials of aldose reductase inhibitors should be restricted to compounds proven to have substantial biological or preclinical advantages over previously tested agents.

PubMed Disclaimer

Conflict of interest statement

CC received consulting fees from Wyeth‐Ayerst, Inc in 1993‐4 for assisting with analysis of nerve biopsies from a clinical trial of tolrestat. TJB has participated in clinical trials utilizing tolrestat sponsored by Wyeth‐Ayerst, zenarestat sponsored by Parke‐Davis, lidorestat sponsored by the Institute for Diabetes Discovery, Inc., and AS 3201 sponsored by Dainippon. TJB received a grant from ICI Pharma to study pre‐clinical effects of ponalrestat.

Figures

1.1
1.1. Analysis
Comparison 1 Change in neurological examination, Outcome 1 Change in neurological examination.
1.2
1.2. Analysis
Comparison 1 Change in neurological examination, Outcome 2 Change in neurological examination, tolrestat alone.
1.3
1.3. Analysis
Comparison 1 Change in neurological examination, Outcome 3 Change in neurological examination, tolrestat, placebo‐controlled studies only.
1.4
1.4. Analysis
Comparison 1 Change in neurological examination, Outcome 4 Change in neurological examination, diabetes duration less than 6 years.
2.1
2.1. Analysis
Comparison 2 Nerve conduction studies, Outcome 1 Change in peroneal motor nerve conduction velocity (m/s).
2.2
2.2. Analysis
Comparison 2 Nerve conduction studies, Outcome 2 Change in peroneal or tibial nerve motor conduction velocity (m/s).
2.3
2.3. Analysis
Comparison 2 Nerve conduction studies, Outcome 3 Change in peroneal compound muscle action potential amplitude (mV).
2.4
2.4. Analysis
Comparison 2 Nerve conduction studies, Outcome 4 Change in sural sensory nerve action potential amplitude (microvolts).
3.1
3.1. Analysis
Comparison 3 Neuropathic symptoms, Outcome 1 Symptoms as dichotomous outcome (same or worse).
3.2
3.2. Analysis
Comparison 3 Neuropathic symptoms, Outcome 2 Symptoms as dichotomous outcome (same or worse), open‐label and non‐placebo‐controlled studies excluded.
3.3
3.3. Analysis
Comparison 3 Neuropathic symptoms, Outcome 3 Change in pain as a continuous variable.
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References

References to studies included in this review

Baba 2006 {published data only}
    1. Baba M, Kimura K‐I, Suda T, Yagihashi S. Three‐year inhibition of aldose reductase on development of symptomatic neuropathy in diabetic patients. Journal of the Peripheral Nervous System 2006;11(2):176‐8. [MEDLINE: ] - PubMed
Boulton 1989 {published data only}
    1. Boulton AJM, Atiea J, Leeuw IH, Lemkes H, MacLeod AF, MacRury S, et al North European Tolrestat Study Group. The efficacy and safety of the aldose‐reductase inhibitor tolrestat in the treatment of chronic sensorimotor diabetic neuropathy. Diabetologia 1989;32:469A. [MEDLINE: ]
Boulton 1990 {published data only}
    1. Boulton AJ, Levin S, Comstock J. A multicentre trial of the aldose‐reductase inhibitor, tolrestat, in patients with symptomatic diabetic neuropathy. Diabetologia 1990;33(7):431‐7. [MEDLINE: ] - PubMed
Brown 2004 {published data only}
    1. Brown MJ, Bird SJ, Watling S, Kaleta H, Hayes L, Eckert S, et al. Natural progression of diabetic peripheral neuropathy in the Zenarestat study population. Diabetes Care 2004;27(5):1153‐9. [MEDLINE: ] - PubMed
Christensen 1987 {published data only}
    1. Christensen JE, Larsen AB, Gregersen G. [Diabetic neuropathy: treatment trial with an aldose reductase inhibitor (Sorbinil)]. [Danish] [Diabetisk neuropati: Behandlingsforsog med en aldosereduktasehaemmer (Sorbinil)]. Ugeskrift for Laeger 1987;149(46):3111‐4. [MEDLINE: ] - PubMed
Daniele 1995 {published data only}
    1. Daniele E, Coco MP. The therapy of diabetic peripheral neuropathy with tolrestat: Is this drug really useful? [Italian] [La terapia della neuropatia diabetica periferica con tolrestat: tale farmaco e realmente utile?]. Clinica Terapeutica 1995;146(12):793‐9. [MEDLINE: ] - PubMed
Dietrich 1990 {published data only}
    1. Dietrich E, Stracke H, Federlin K. The effects of the aldose reductase inhibitor 'Statil' on diabetic peripheral neuropathy. Diabetologia 1990;33:A167. [MEDLINE: ]
Fabiani 1995 {published data only}
    1. Fabiani F, Vincentis N, Staffilano A. Effect of Tolrestat on oesophageal transit time and cholecystic motility in type 2 diabetic patients with asymptomatic diabetic neuropathy. Diabete et Metabolisme 1995;21(5):360‐4. [MEDLINE: ] - PubMed
Faes 1993 {published data only}
    1. Faes TJ, Yff GA, DeWeerdt O, Lanting P, Heimans JJ, Bertelsmann FW. Treatment of diabetic autonomic neuropathy with an aldose reductase inhibitor. Journal of Neurology 1993;240(3):156‐60. [MEDLINE: ] - PubMed
Fagius 1985 {published data only}
    1. Fagius J, Brattberg A, Jameson S, Berne C. Limited benefit of treatment of diabetic polyneuropathy with an aldose reductase inhibitor: A 24‐week controlled trial. Diabetologia 1985;28(6):323‐9. [MEDLINE: ] - PubMed
Florkowski 1990 * {published data only}
    1. Florkowski CM, Rowe BR, Nightingale S, Barnett AH. A six‐month randomized placebo‐controlled trial of the aldose reductase inhibitor ponalrestat in chronic symptomatic peripheral neuropathy. International Diabetes Federation Symposium on Diabetic Neuropathy , Sydney, Australia. Chichester: John Wiley and Sons, 1990:143‐8.
Florkowski 1991 {published data only}
    1. Florkowski CM, Rowe BR, Nightingale S, Harvey TC, Barnett AH. Clinical and neurophysiological studies of aldose reductase inhibitor ponalrestat in chronic symptomatic diabetic peripheral neuropathy. Diabetes 1991;40(1):129‐133. [MEDLINE: ] - PubMed
Giugliano 1993 {published data only}
    1. Giugliano D, Marfella R, Quatraro A, Rosa N, Salvatore T, Cozzolino D, Ceriello A, Torella R. Tolrestat for mild diabetic neuropathy: A 52‐week, randomized, placebo‐ controlled trial. Annals of Internal Medicine 1993;118(1):7‐11. [MEDLINE: ] - PubMed
Giugliano 1995 {published data only}
    1. Giugliano D, Acampora R, Marfella R, Maro G, Rosa N, Misso L, et al. Tolrestat in the primary prevention of diabetic neuropathy. Diabetes Care 1995;18(4):536‐41. [MEDLINE: ] - PubMed
Greene 1999 {published data only}
    1. Greene DA, Arezzo JC, Brown MB, Zenarestat Study Group. Effect of aldose reductase inhibition on nerve conduction and morphometry in diabetic neuropathy [erratum appears in Neurology 2001;56(8):1124]. Neurology 1999;53(3):580‐91. [MEDLINE: ] - PubMed
Guy 1988 {published data only}
    1. Guy RJ, Gilbey SG, Sheehy M, Asselman P, Watkins PJ. Diabetic neuropathy in the upper limb and the effect of twelve months sorbinil treatment. Diabetologia 1988;31(4):214‐20. [MEDLINE: ] - PubMed
Hotta 2001 {published data only}
    1. Hotta N, Toyota T, Matsuoka K, Shigeta Y, Kikkawa R, Kaneko T, et al The SNK‐860 Diabetic Neuropathy Study Group. Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52‐week multicenter placebo‐controlled double‐blind parallel group study. Diabetes Care 2001;24(10):1776‐82. [MEDLINE: ] - PubMed
Hotta 2006 {published data only}
    1. Hotta N, Akanuma Y, Kawamori R, Matsuoka K, Oka Y, Shichiri M, et al The ADCT Study Group. Long‐term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic periheral neuropathy: The 3‐year, multicenter, comparative aldose reductase inhibitor‐diabetes complications trial. Diabetes Care 2006;29(7):1538‐44. - PubMed
Jennings 1990 {published data only}
    1. Jennings PE, Nightingale S, Guen C, Lawson N, Williamson JR, Hoffman P, et al. Prolonged aldose reductase inhibition in chronic peripheral diabetic neuropathy: effects on microangiopathy. Diabetic Medicine 1990;7(1):63‐8. [MEDLINE: ] - PubMed
Jespersen 1986 {published data only}
    1. Jespersen J, Gram J, Christensen JE. Neurophysiological variables and fibrinolysis in insulin‐dependent diabetes treated with an aldose reductase inhibitor or placebo. A double‐blind randomized study. Haemostasis 1986;16(6):453‐7. [MEDLINE: ] - PubMed
Johnson 2004 {published data only}
    1. Johnson BF, Nesto RW, Pfeifer MA, Slater WR, Vinik AI, Chyun DA, Law G, Wackers FJ, Young LH. Cardiac abnormalities in diabetic patients with neuropathy: effects of aldose reductase inhibitor administration. Diabetes Care 2004;27(2):448‐54. [MEDLINE: ] - PubMed
Krentz 1992 {published data only}
    1. Krentz AJ, Honigsberger L, Ellis SH, Hardman M, Nattrass M. A 12‐month randomized controlled study of the aldose reductase inhibitor ponalrestat in patients with chronic symptomatic diabetic neuropathy. Diabetic Medicine 1992;9(5):463‐8. [MEDLINE: ] - PubMed
Macleod 1992 {published data only}
    1. Macleod AF, Boulton AJ, Owens DR, Rooy P, Gerven JM, MacRury S, et al North European Tolrestat Study Group. A multicentre trial of the aldose‐reductase inhibitor tolrestat in patients with symptomatic diabetic peripheral neuropathy. Diabetes & Metabolism 1992;18(1):14‐20. [MEDLINE: ] - PubMed
Martyn 1987 {published data only}
    1. Martyn CN, Reid W, Young RJ, Ewing DJ, Clarke BF. Six‐month treatment with sorbinil in asymptomatic diabetic neuropathy. Failure to improve abnormal nerve function. Diabetes 1987;36(9):987‐90. [MEDLINE: ] - PubMed
Nakayama 2001 {published data only}
    1. Nakayama M. Aldose reductase inhibition ameliorates pupillary light reflex and F‐wave latency in patients with mild diabetic neuropathy. Diabetes Care 2001;24(6):1093‐1098. [MEDLINE: ] - PubMed
O'Hare 1988 {published data only}
    1. O'Hare JP, Morgan MH, Alden P, Chissel S, O'Brien IA, Corrall RJ. Aldose reductase inhibition in diabetic neuropathy: clinical and neurophysiological studies of one year's treatment with sorbinil. Diabetic Medicine 1988;5(6):537‐42. [MEDLINE: ] - PubMed
Salmon 1991 {published data only}
    1. Salmon P, Perkins CM, Tomkin GH. Diabetic neuropathy and aldose reductase inhibition. Diabetes, Nutrition & Metabolism ‐ Clinical & Experimental 1991;4(2):135‐39. [MEDLINE: ]
Sima 1988 {published data only}
    1. Sima AAF, Bril V, Nathaniel V, McEwen TAJ, Brown MB, Lattimer SA, et al. Regeneration and repair of myelinated fibers in sural‐nerve biopsy specimens from patients with diabetic neuropathy treated with sorbinil. New England Journal of Medicine 1988;319(9):548‐55. [MEDLINE: ] - PubMed
SRG 1993 {published data only}
    1. Sorbinil Retinopathy Trial Research Group. The sorbinil retinopathy trial: neuropathy results. Neurology 1993;43(6):1141‐9. [MEDLINE: ] - PubMed
Stracke 1994 {published data only}
    1. Stracke H, Dietrich E. Influence of Ponalrestat, an aldose‐reductase inhibitor, on diabetic polyneuropathy. [German] [Der Einfluss des Aldose‐Reduktase‐Inhibitors Ponalrestat auf die diabetische Polyneuropathie]. Medizinische Welt 1994;45(3):84‐89. [MEDLINE: ]
Sundkvist 1992 {published data only}
    1. Sundkvist G, Armstrong FM, Bradbury JE, Chaplin C, Ellis SH, Owens DR, et al. Peripheral and autonomic nerve function in 259 diabetic patients with peripheral neuropathy treated with ponalrestat (an aldose reductase inhibitor) or placebo for 18 months. Journal of Diabetes and its Complications 1992;6(2):123‐30. [MEDLINE: ] - PubMed
van Gerven 1992 {published data only}
    1. Gerven JM, Lemkes HH, Dijk JG. Long‐term effects of tolrestat on symptomatic diabetic sensory polyneuropathy. Journal of Diabetes and its Complications 1992;6(1):45‐8. [MEDLINE: ] - PubMed
van Gerven 1993 * {published data only}
    1. Gerven JM. Further clinical studies with an aldose reductase inhibitor in diabetic neuropathy. Diabetic Medicine 1993;10(Suppl):38S. [MEDLINE: ] - PubMed
Ziegler 1991 {published data only}
    1. Ziegler D, Mayer P, Rathmann W, Gries FA. One‐year treatment with the aldose reductase inhibitor, ponalrestat, in diabetic neuropathy. Diabetes Research and Clinical Practice 1991;14(1):63‐73. [MEDLINE: ] - PubMed

References to studies excluded from this review

Bertelsmann 1991 {published data only}
    1. Bertelsmann FW, Faes ThJC, Weerdt O, Yff GA, Heimans JJ, Lanting P. Treatment of diabetic autonomic neuropathy with the aldose reductase inhibitor statil. Diabetologia 1991;34(Suppl 2):A37. [MEDLINE: ]
Bril 2006 {published data only}
    1. Bril V, Buchanan RA. Long‐term effects of ranirestat (AS‐3201) on peripheral nerve function in patients with diabetic sensorimotor polyneuropathy. Diabetes Care 2006;29(1):68‐72. - PubMed
Canal 1984 {published data only}
    1. Canal N, Comi G, Marchettini P, Pozza G. Effects of cyclandelate on diabetic peripheral neuropathy. British Journal of Clinical Practice. Supplement 1984;34:62‐8. [MEDLINE: ] - PubMed
Fagius 1981 {published data only}
    1. Fagius J, Jameson S. Effects of aldose reductase inhibitor treatment in diabetic polyneuropathy ‐ a clinical and neurophysiological study. Journal of Neurology, Neurosurgery and Psychiatry 1981;44(11):991‐1001. [MEDLINE: ] - PMC - PubMed
Gianni 1992 {published data only}
    1. Gianni G, Vismara V, Borsini W, Castellani G, Marcacci G. Treatment of diabetic neuropathy by tolrestat. [Italian] [Trattamento con tolrestat nella neuropatia diabetica]. Rivista di Neurobiologia 1992;38(5):321‐24. [MEDLINE: ]
Gonen 1991 {published data only}
    1. Gonen B, Bochenek W, Beg M, Graepel J, Tolrestat Study Group. The effect of withdrawal of tolrestat, an aldose reductase inhibitor, on signs, symptoms and nerve function in diabetic neuropathy. Diabetologia 1991;34:A153. [MEDLINE: ]
Goto 1993 {published data only}
    1. Goto Y, Hotta N, Shigeta Y, Sakamoto N, Kito S, Matsuoka K, et al. A placebo‐controlled double‐blind study of epalrestat (ONO‐2235) in patients with diabetic neuropathy. Diabetic Medicine 1993;10(SUPPL. 2):39S‐43S. [MEDLINE: ] - PubMed
Greene 1989 {published data only}
    1. Greene DA, Porte D, Bril V, Clements RS, Shamoon H, Ziedler A, Peterson MJ, Munster E, Pfeifer MA, Sorbinil Neuropathy Study Group. Clinical response to sorbinil treatment in diabetic neuropathy. Diabetologia 1989;32:493A. [MEDLINE: ]
Guigliano 1991 {published data only}
    1. Giugliano D, Marfella R, Salvatore T, Cozzolino D, Quatraro A, Bianchi C, Torella R. A double‐blind controlled study on the effect of tolrestat on diabetic autonomic neuropathy. Diabetologia 1991;34:A152. [MEDLINE: ]
Jaspan 1983 {published data only}
    1. Jaspan J, Maselli R, Herold K, Bartkus C. Treatment of severely painful diabetic neuropathy with an aldose reductase inhibitor: relief of pain and improved somatic and autonomic nerve function. Lancet 1983;2(8353):758‐62. [MEDLINE: ] - PubMed
Santiago 1993 {published data only}
    1. Santiago JV, Snksen PH, Boulton AJ, Macleod A, Beg M, Bochenek W, et al. Withdrawal of the aldose reductase inhibitor tolrestat in patients with diabetic neuropathy: effect on nerve function. Journal of Diabetes and its Complications 1993;7(3):170‐8. [MEDLINE: ] - PubMed
Sima 1993 {published data only}
    1. Sima AA, Greene DA, Brown MB, Hohman TC, Hicks D, Graepel GJ, et al. Effect of hyperglycemia and the aldose reductase inhibitor tolrestat on sural nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy. Journal of Diabetes and its Complications 1993;7(3):157‐69. [MEDLINE: ] - PubMed
Terranova 1993 {published data only}
    1. Terranova R, Luca S. [Treatment with an aldose reductase inhibitor in peripheral neuropathy in elderly diabetic patients]. [Italian]. Minerva Medica 1993;84(9):461‐66. [MEDLINE: ] - PubMed
Young 1983 {published data only}
    1. Young RJ, Ewing DJ, Clarke BF. A controlled trial of sorbinil, an aldose reductase inhibitor, in chronic painful diabetic neuropathy. Diabetes 1983;32(10):938‐42. [MEDLINE: ] - PubMed

References to studies awaiting assessment

Nakajima 2005 {published data only}
    1. Nakajima T, Fukui M, Deguchi M, Tanaka T, Tegoshi H, Hashimoto M, Tsubouchi Y, Hasegawa G, Nakamura N. Efficacy of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy in a crossover trial. Journal of the Japan Diabetes Society 2005;48(8):601‐6.

Additional references

Abbott 1998
    1. Abbott CA, Vileikyte L, Williamson S, Carrington AL, Boulton AJM. Multicenter study of the incidence of and predictive risk factors for diabetic neuropathic foot ulceration. Diabetes Care 1998;21(7):1071‐5. [MEDLINE: ] - PubMed
Cameron 1997
    1. Cameron NE, Cotter MA. Metabolic and vascular factors in the pathogenesis of diabetic neuropathy. Diabetes 1997;46(Suppl 2):S31‐7. [MEDLINE: ] - PubMed
DCCTRG 1993
    1. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long‐term complications in insulin‐dependent diabetes mellitus. New England Journal of Medicine 1993;329(14):977‐86. - PubMed
Dyck 1989
    1. Dyck PJ. Hypoxic neuropathy: Does hypoxia play a role in diabetic neuropathy?. Neurology 1989;39(1):111‐8. [MEDLINE: ] - PubMed
Dyck 1997
    1. Dyck PJ, Davies JL, Litchy WJ, O'Brien PC. Longitudinal assessment of diabetic polyneuropathy using a composite score in the Rochester Diabetic Neuropathy Study cohort. Neurology 1997;49(1):229‐39. [MEDLINE: ] - PubMed
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. British Medical Journal 1997;315(7109):629‐34. - PMC - PubMed
Hamada 2004
    1. Hamada Y, Nakamura J. Clinical potential of aldose reductase inhibitors in diabetic neuropathy. Treatments in Endocrinology 2004;3(4):245‐255. - PubMed
Leinninger 2006
    1. Leinninger GM, Edwards JL, Lipshaw MJ, Feldman EL. Mechanisms of disease: mitochondria as new therapeutic targets in diabetic neuropathy. Nature Clinical Practice Neurology 2006;2(11):620‐8. - PubMed
Mayfield 1998
    1. Mayfield JA, Reiber GE, Sanders LJ, Janisse D, Pogach LM. Preventive foot care in people with diabetes. Diabetes Care 1998;21(12):2161‐77. [MEDLINE: ] - PubMed
Nicolucci 1996
    1. Nicolucci A, Carinci F, Cavaliere D, Scorpiglione N, Belfiglio M, Labbrozzi D, et al. A meta‐analysis of trials on aldose reductase inhibitors in diabetic peripheral neuropathy. The Italian Study Group. The St. Vincent Declaration. Diabetic Medicine 1996;13(12):1017‐26. - PubMed
Oates 2002
    1. Oates PJ. Polyol pathway and diabetic peripheral neuropathy. International Review of Neurobiology 2002;50:325‐92. [MEDLINE: ] - PubMed
Shaw 2003
    1. Shaw JE, Zimmet PZ, Gries FA, Ziegler D. Epidemiology of Diabetic Neuropathy. In: Gries FA, Cameron NE, Low PA, Ziegler D editor(s). Textbook of Diabetic Neuropathy. New York: Thieme, 2003:64‐82.
Ziegler 2006
    1. Ziegler D. Treatment of diabetic polyneuropathy: Update 2006. Annals of the New York Academy of Sciences 2006;1084:250‐66. - PubMed

References to other published versions of this review

Airey 1997
    1. Airey M, Bennett C, Nicolucci A, Williams R. Aldose reductase inhibitors for the prevention and treatment of diabetic peripheral neuropathy. Cochrane Database of Systematic Reviews 1997, Issue 2. - PMC - PubMed

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