Evaluation of efficacy and safety of epalrestat and epalrestat in combination with methylcobalamin in patients with diabetic neuropathy in a randomized, comparative trial

Manish Maladkar, N. J. S. Saggu, P. Moralwar, Aziz A. Mhate, Datta Zemse, Anil Bhoraskar

23-A Shah Industrial Estate, Andheri, India.
Bhalchandra Niwas, Mumbai, India.
F-1, Dattaguru Co-Operative Society, Mumbai, India.
M.G.M. Hospital, Mumbai, India.
Mhate Clinic, B-3, Sector 2, Mumbai, India.
Moralwar Day Care Centre, Sector 1-A, Mumbai, India.

DOI: 10.4236/jdm.2013.31004                

Abstract

Recent Background: Diabetic neuropathy is one of the major complications in long standing hyperglycemic patients. Though exact mechanism of neuronal damage is unclear, accumulation of excess sorbitol through polyol pathway is believed to contribute significantly. Epalrestat and methylcobalamin are extensively used in this area to counter neuronal damage. This study was aimed to evaluate the combined effect of these drugs. Materials and Methods: A total of 220 patients with diabetic neuropathy were included in this study. The patients were divided into two groups; group A was administered combination of epalrestat 50 mg and methylcobalamin 500 mcg while group B was administered epalrestat 50 mg alone (both thrice daily). The treatment period was 12 weeks with monitoring on week 4, 8 and 12 of the study. At baseline and at follow up visits following parameters were evaluated: loss of sensation, burning sensation, numbness, muscle cramps, spontaneous pain, weakness, dizziness, loss of the thermal sensitivity, tendon reflexes, muscle strength and pain intensity using visual analog scale (VAS). Results: All the parameters were improved in both the groups compared to baseline. In group A significant improvement was seen on week 4 itself and continued for the rest of the study in all the measured parameters. Group B showed significant improvement from 8th week onwards. The inter-group difference is statistically significant in favour of the combination therapy. Conclusion: Combination of epalrestat and methylcobalamin is a better option for the treatment of diabetic neuropathy than epalrestat alone. Combination therapy was associated with faster onset and better symptomatic relief.

Keywords

Epalrestat; Methylcobalamin; Diabetic Neuropathy

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Peeraer, E., Van Lutsenborg, A., Verheyen, A., De Jongh, R., Nuydens, R. and Meert, T.F. (2011) Pharmacological evaluation of rat dorsal root ganglion neurons as an in vitro model for diabetic neuropathy. Journal of Pain Research, 4, 55-65. doi:10.2147/JPR.S15452
[2]	Ramachandran, A., Snehalatha, C., Vijay, V. and Vishwanathan, M. (1996) Diabetic retinopathy at the time of diagnosis of NIDDM in South Indian subjects. Diabetes Research and Clinical Practice, 32, 111-114. doi:10.1016/0168-8227(96)01185-0
[3]	Chihiro, Y.N. (1998) Aldose reductase in glucose toxicity: A potential target for the prevention of diabetic complications. Pharmacological Reviews, 50, 21-33.
[4]	Itagaki, I., Shimizu, K., Kamanaka, Y., Ebata, K., Kikkawa, R., Haneda, M. and Shigeta, Y. (1994) The effect of an aldose reductase inhibitor (epalrestat) on diabetic nephropathy in rats. Diabetes Research and Clinical Practice, 25, 147-154. doi:10.1016/0168-8227(94)90002-7
[5]	Hotta, N., Kakuta, H., Koh, N., Fukasawa, H., Yasuma, T., Awaya, S. and Sakamoto, N. (1991) In vitro retinal and erythrocyte polyol pathway regulation by hormones and an aldose reductase inhibitor. Diabetes Research and Clinical Practice, 14, 29-35. doi:10.1016/0168-8227(91)90050-N
[6]	Ramirez, M.A. and Borja, N.L. (2008) Epalrestat: An aldose reductase inhibitor for the treatment of diabetic neuropathy. Pharmacotherapy, 28, 646-655. doi:10.1592/phco.28.5.646
[7]	Sharma, S.R. and Sharma, N. (2008) Epalrestat, an aldose reductase inhibitor, in diabetic neuropathy: An Indian perspective. Annals of Indian Academy Neurology, 11, 231-235. doi:10.4103/0972-2327.44558
[8]	Yaqub, B.A., Siddique, A. and Sulimani, R. (1992) Effects of methylcobalamin on diabetic neuropathy. Clinical Neurology and Neurosurgery, 94, 105-111. doi:10.1016/0303-8467(92)90066-C
[9]	Sun, Y., Lai, M.S. and Lu, C.J. (2005) Effectiveness of vitamin B12 on diabetic neuropathy: Systematic review of clinical controlled trials. Acta Neurologica Taiwanica, 14, 48-54.
[10]	Maladkar, M., Rajadhyaksha, G., Venkatswamy, N., Hariharan, R.S. and Lohati, S.R. (2009) Efficacy, safety and tolerability of epalrestat compared to methylcobalamin in patients with diabetic neuropathy. International Journal of Diabetes in Developing Countries, 29, 28-34. doi:10.4103/0973-3930.50712