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Metformin is one of the most widely used oral antihyperglycemic agents. Adverse effect of metformin is disturbance in vitamin B12 metabolism associated with low serum vitamin B12 level. Vitamin B12 hypovitaminosis is accompanied by peripheral neuropathy. The long-term use can cause anemia and increase the risk of depression, cerebrovascular and neurodegenerative diseases. Clinical studies and meta-analyses have constantly confirmed the association between metformin use and vitamin B12 hypovitaminosis. It was shown that every 25 pmol/l increase in B12 level was associated with a 6% reduction in the risk of neuropathy. The application of B12 would help compensate the disturbances in vitamin B12 metabolism caused by metformin.
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Wong CW, Leung CS, Leung CP, Cheng JN. Association of metformin use with vitamin B12 deficiency in the institutionalized elderly. Arch Gerontol Geriatr. 2018 Nov - Dec;79:57-62. doi: 10.1016/j.archger.2018.07.019.
Xu L, Huang Z, He X, Wan X, Fang D, Li Y. Adverse effect of metformin therapy on serum vitamin B12 and folate: short-term treatment causes disadvantages? Med Hypotheses. 2013 Aug;81(2):149-51. doi: 10.1016/j.mehy.2013.05.025.
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.
Sahin M, Tutuncu NB, Ertugrul D, Tanaci N, Guvener ND. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complications. 2007 Mar-Apr;21(2):118-23. doi: 10.1016/j.jdiacomp.2005.10.005.
Zdilla MJ. Metformin With Either Histamine H2-Receptor Antagonists or Proton Pump Inhibitors: A Polypharmacy Recipe for Neuropathy via Vitamin B12 Depletion. Clin Diabetes. 2015 Apr;33(2):90-5. doi: 10.2337/diaclin.33.2.90.
Damiao CP, Rodrigues AO, Pinheiro MF, et al. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J. 2016 Nov-Dec;134(6):473-479. doi: 10.1590/1516-3180.2015.01382111.
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.
Andres E, Perrin AE, Demangeat C et al. The syndrome of food-cobalamin malabsorption revisited in a department of internal medicine. A monocentric cohort study of 80 patients. Eur J Intern Med. 2003 Jul;14(4):221-226.
Hansen CS, Jensen JS, Ridderstrale M, Vistisen D, Jørgensen 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.
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. doi: 10.1186/s40360-016-0088-3.
Wulffele MG, Kooy A, Lehert P, et al. Effects of short-term treatment with metformin on serum concentrations of homoc.ysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2003 Nov;254(5):455-63.
Kancherla V, Garn JV, Zakai NA, et al. Multivitamin Use and Serum Vitamin B12 Concentrations in Older-Adult Metformin Users in REGARDS, 2003–2007. PLoS One. 2016 Aug 11;11(8):e0160802. doi: 10.1371/journal.pone.0160802.
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.
Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016 Apr;101(4):1754-61. doi: 10.1210/jc.2015-3754.
Parry-Strong A, Langdana F, Haeusler S, Weatherall M, Krebs J. Sublingual vitamin B12 compared to intramuscular injection in patients with type 2 diabetes treated with metformin: a randomised trial. N Z Med J. 2016 Jun 10;129(1436):67-75.
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.