Effect of metformin on serum level of vitamin B12 and folate in patients of type-2 diabetes mellitus
Keywords:Type 2 diabetes mellitus, Metformin, Vitamin B12, MCV, Serum folate
Background: Several types of DM are caused by a complex interaction of genetic and environmental factors. Depending on the etiology of the DM, factors contributing to hyperglycaemia include- reduced insulin secretion, decreased glucose utilization, and increased glucose production.Objective of the current study was to study the effect of metformin on the level of vitamin B12 and folate in patients of type 2 DM.
Methods: This is hospital based study before and after metformin therapy randomized controlled trial was conducted in medicine ward of M. B. hospital, Udaipur. Baseline serum vitamin B12 and folate level of all patients were measured and treatment with metformin 500 mg twice a day was given for 6 months. After 6 months serum vitamin B12 and folate level of all patients were re-evaluated.
Results: There was a significant positive correlation (r=0.824, p<0.001) between decrease in vitamin B12 and decrease in folate level after metformin treatment. When analysis for change in vitamin B12 is compared with change in MCV values after 6 months, negative correlation (r=-0.08, p>0.05) was obtained. A non significant correlation (r=-0.08, p>0.05) with change in level of serum folate and change in MCV values or haemoglobin level was obtained.
Conclusions: Low serum vitamin B12 level is associated with longer duration and higher dose of metformin use. Routine determination of vitamin B12 level in patients with type 2 DM on high dose of metformin and those with prolonged use of metformin might help in identifying patients that would benefit from vitamin B12 supplements.
Alvin CP. Diabetes Mellitus In: Harrison TR, Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL. Harrison’s Principles of internal medicine. 18th ed. New York; McGraw Hill: 2011.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2008;31(1):s55-60.
American Diabetes Association. Diagnosis and classification of diabetes Mellitus. Diabetes Care. 2009;32(1): s62-7.
David MN, John BB, Mayer BD, Ele F, Rury RH. Medical management of hyperglycaemia in type2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the american diabetes association and the european association for the study of diabetes. Diabetes Care. 2009;1:193-203.
UK prospective diabetes study group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complication in patients with type2 diabetes (UKPDS 33). Lancet. 1998;352: 837-53.
UK prospective diabetes study (UKPDS) Group. Effect of intensive blood glucose control with metformin on complication in overweight patients with type2 diabetes. Lancet. 1998;352:854-65.
Bailey CJ, Turner RC. Metformin. N Engl J Med. 1992;334:574-83.
DeFronzo R, Goodman A. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med. 1995;333:541-9.
Diabetes prevention program research group. Long-term safety, tolerability, and weight loss associated with metformin in the diabetes prevention program outcomes study. Diabetes care. 2012;35(4):731-7.
Jolien de J, Adriaan K, Philippe L, Michiel GW, Kolk J, Daniël B, et al. Long term treatment with metformin in patients with type2 diabetes and risk of vitamin B12 deficiency: randomised placebo controlled trial. BMJ. 2010;340:c2181.
Wulffelé MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, et al. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate, and vitamin B12 in type2 diabetes mellitus: a randomized, placebo controlled trial. J Intern Med. 2003;254: 455-63.
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 Comp. 2007;21(2):118-23.
Pongchaidecha M, Srikusalanukul V, Chattananon A, Tanjariyaporn S. Effect of metformin on plasma homocysteine, vitamin B12 and folic acid: a cross-sectional study in patients with type 2 diabetes mellitus. J Med Assoc Thai. 2004;87(7):780-7.
Kim J, Ahn CW, Fang S, Lee HS, Park JS. Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes. Medicine (Baltimore). 2019;98(46):e17918.
Sara F, Sobia N. A Review on effects of metformin on vitamin B12 status. Am J Phytomed Clin Ther. 2013;1(8):652-60.