Influence of methylcobalamin on the vitamin B12 level and manifestations of neuropathy in patients with type 2 diabetes mellitus and metformin-associated vitamin B12 deficiency


  • V.I. Pankiv MD, PhD, Professor, Ukrainian Research and Practical Centre of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine, Kyiv, Ukraine; e-mail:; Web of Science ResearcherID O-6794-2018



type 2 diabetes mellitus, metformin, B12 hypovitaminosis, neuropathy, methylcobalamin


Background. Adverse side effect of metformin is disturbance in vitamin B12 metabolism associated with low serum vitamin B12 level. B12 hypovitaminosis is accompanied by peripheral neuropathy. The aim of the study was to determine the effectiveness of methylcobalamin (Diacobal preparation manufactured by Kusum Pharm LLC, Ukraine) in correcting vitamin B12 deficiency in diabetic patients with metformin­associated vitamin B12 deficiency, and to establish its effect on manifestations of diabetic neuropathy. Materials and methods. Thirty patients with type 2 diabetes mellitus and metformin­associated vitamin B12 deficiency (< 190 pg/ml) were examined. Duration of metformin administration was 6.1 years on average, the average dose was 2100 mg/day. Methylcobalamin was administered at a dose of 500 mg three times a day for three months. Determination of vitamin B12 content and assessment of neuropathy manifestations was carried out before and after the course of treatment. Results. After the course of treatment, it was found that the average content of vitamin B12 in the blood serum reached the reference values (312.4 ± 39.8 pg/ml). The positive effect of therapy on the severity of clinical manifestations of peripheral sensory motor neuropathy in the examined patients was revealed: in 17 (56.7 %) patients, the severity of numbness in feet significantly decreased, in 6 (20 %) persons, there was a complete disappearance of numbness. The intensity of the pain syndrome decreased in 19 (63.3 %) patients, the pain syndrome was completely removed in 3 (10 %) persons. Conclusions. The relationship between metformin and B12 hypovitaminosis has been confirmed. Diacobal is an effective and safe drug for the prevention and treatment of metformin­induced vitamin B12 deficiency and diabetic neuropathy.


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Flory J, Lipska K. Metformin in 2019. JAMA. 2019 Apr 22. doi: 10.1001/jama.2019.3805.

Yang W, Cai XL, Wu H, Ji L. Associations between metformin use and vitamin B12 level, anemia and neuropathy in patients with diabetes: a meta-analysis. J Diabetes. 2019 Jan 7. doi: 10.1111/1753-0407.12900.

Chapman LE, Darling AL, Brown JE. Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab. 2016 Nov;42(5):316-327. doi: 10.1016/j.diabet.2016.03.008.

Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP Jr. Association of biochemical B₁₂ deficiency with metformin therapy and vitamin B₁₂ supplements: the National Health and Nutrition Examination Survey, 1999-2006. Diabetes Care. 2012 Feb;35(2):327-33. doi: 10.2337/dc11-1582.

Greibe E, Miller JW, Foutouhi SH, Green R, Nexo E. Metformin increases liver accumulation of vitamin B12 – an experimental study in rats. Biochimie. 2013 May;95(5):1062-5. doi: 10.1016/j.biochi.2013.02.002.

Roy RP, Ghosh K, Ghosh M, et al. Study of Vitamin B12 deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus. Indian J Endocrinol Metab. 2016 Sep-Oct;20(5):631-637. doi: 10.4103/2230-8210.190542.

Niafar M, Hai F, Porhomayon J, Nader ND. The role of metformin on vitamin B12 deficiency: a meta-analysis review. Intern Emerg Med. 2015 Feb;10(1):93-102. doi: 10.1007/s11739-014-1157-5.

Hansen CS, Jensen JS, Ridderstrale M, Vistisen D, Jorgensen ME, Fleischer J. Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes. J Diabetes Complications. 2017 Jan;31(1):202-208. doi: 10.1016/j.jdiacomp.2016.08.025.

Biemans E, Hart HE, Rutten GE, Cuellar Renteria VG, Kooijman-Buiting AM, Beulens JW. Cobalamin status and its relation with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin. Acta Diabetol. 2015 Apr;52(2):383-93. doi: 10.1007/s00592-014-0661-4.

Beulens JW, Hart HE, Kuijs R, Kooijman-Buiting AM, Rutten GE. Influence of duration and dose of metformin on cobalamin deficiency in type 2 diabetes patients using metformin. Acta Diabetol. 2015 Feb;52(1):47-53. doi: 10.1007/s00592-014-0597-8.

Ahmed MA, Muntingh G, Rheeder P. Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy. BMC Pharmacol Toxicol. 2016 Oct 7;17(1):44.

Introduction: Standards of Medical Care in Diabetes – 2019. Diabetes Care. 2019 Jan;42(Suppl 1):S1-S2. doi: 10.2337/dc19-Sint01.



How to Cite

Pankiv, V. (2021). Influence of methylcobalamin on the vitamin B12 level and manifestations of neuropathy in patients with type 2 diabetes mellitus and metformin-associated vitamin B12 deficiency. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), 15(4), 317–321.



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