Meta-analysis of methylcobalamin alone and in combination with lipoic acid in patients with diabetic peripheral neuropathy

Diabetes Res Clin Pract. 2013 Aug;101(2):99-105. doi: 10.1016/j.diabres.2013.03.033. Epub 2013 May 9.


Aims: To compare the efficacy and safety of daily lipoic acid (300-600 mg i.v.) plus methylcobalamin (500-1000 mg i.v. or im.) (LA-MC) with that of methylcobalamin alone (MC) on diabetic peripheral neuropathy (DPN).

Methods: Electronic database were searched for studies published up to November 1, 2012 and study quality was assessed in duplicate. A random or a fixed effect model was used to analyse outcomes which were expressed as risk ratios (RRs) or mean difference (MD). I(2) statistic was used to assess heterogeneity.

Results: Seventeen studies were included. Combined data from all studies showed that the LA-MC combination therapy was significantly superior to MC monotherapy (RR=1.47; 95% CI: 1.37-1.58). Superiority of the LA-MC combination was shown in nerve conduction velocity (NCV) with WMDs of 6.89 (95% CI: 4.24-9.73) for median motor nerve conduction velocity (MNCV), 5.24 (4.14-6.34) for median sensory nerve conduction velocity (SNCV), 4.34 (3.03-5.64) for peroneal MNCV, and 4.53 (3.2-5.85) for peroneal SNCV. There were no serious adverse events associated with treatment.

Conclusions: The results of the meta-analysis show that treatment with LA-MC for 2-4 weeks is associated with better outcomes in NCV and neuropathic symptoms relative to MC treatment. However larger well-designed studies are required to confirm this conclusion.

Keywords: Combination therapy; Diabetic peripheral neuropathy; Lipoic acid; Meta-analysis; Methylcobalamin.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Diabetic Neuropathies / drug therapy*
  • Drug Therapy, Combination
  • Humans
  • Peripheral Nervous System Diseases / drug therapy*
  • Thioctic Acid / therapeutic use*
  • Vitamin B 12 / analogs & derivatives*
  • Vitamin B 12 / therapeutic use


  • Thioctic Acid
  • mecobalamin
  • Vitamin B 12