Published: 2020-08-25

Serum vitamin B12 and homocysteine levels in type 2 diabetes patients on metformin

Kunal Lala, Divya Lala, Saurabh Duggad


Background: Metformin is reported to induce vitamin B12 deficiency, however India data is limited. The present study was conducted to assess the vitamin B12 and homocysteine levels among type 2 diabetes mellitus patients taking metformin.

Methods: The present observational study included 60 patients with diabetes mellitus, 30 patients on metformin therapy (at least 6 months) and 30 patients not on metformin use. Laboratory investigations were sent for vitamin B12, homocysteine and HbA1c.

Results: Mean vitamin B12 level was 159.67±95.73 and 510.73±206.18 pmol/l in the metformin and non-metformin group respectively (p value <0.001). Serum homocysteine levels were found to significantly higher in the metformin group as compared to non-metformin group (17.39±4.97 vs 14.43±2.43 µmol/l, p value <0.01). Folate levels were similar in the two study groups (22.71±3.67 vs 27.54±2.83 mmol/L). Haemoglobin A1c levels were significantly higher in the metformin group as compared to non-metformin group (7.85±0.97 vs 7.25±0.80 respectively). Triglycerides, high density lipoprotein and total cholesterol levels were found to be similar between the two study groups. However, low density lipoproteins were significantly higher in the metformin group as compared to the non-metformin group (3.7±0.92 vs 3.4±0.86 mmol/l).

Conclusions: Our results show metformin use in type 2 diabetes mellitus patients was associated with significantly lower vitamin B12 levels and significantly high homocysteine levels. 


Diabetes mellitus, Homocysteine, Metformin, Vitamin B12

Full Text:



Group UPDS. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). The Lancet. 1998;352(9131):854–65.

American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care. 2016.

Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V. Increased intake of calcium reverses vita- min B12 malabsorption induced by metformin. Diabetes care. 2000;23(9):1227-31.

Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, Bouter LM, et al. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non–insulin-dependent diabetes mellitus a population based study. Arteriosclerosis, Thrombosis Vascular Biology. 1998;18(1):133-8.

Liu F, Mao JP, Yan X. Toronto clinical scoring system in diabetic peripheral neuropathy. Zhong nan da xue xue bao. Yi xue ban= J Central South University. Medical Sciences. 2008;33(12):1137-41.

Carmel R, Green R, Rosenblatt DS, Watkins D. Update on cobalamin, folate, and homocysteine. Hematology Am Soc Hematol Educ Program. 2003:62-81.

Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP Jr. Association of biochemical B12 de ciency with metformin therapy and Vitamin B12 supplements: The National Health and Nutrition Examination Survey, 1999-2006. Diabetes Care. 2012;35:327-33.

Raizada N, Jyotsna VP, Sreenivas V, Tandon N. Serum vitamin B12 levels in type 2 diabetes patients on metformin compared to those never on metformin: a cross-sectional study. Indian J Endocrinol Metabol. 2017;21(3):424.

Chapman LE, Darling AL, Brown JE. Association between metformin and Vitamin B (12) de ciency in patients with type 2 diabetes: A systematic review and meta-analysis. Diab Metabol. 2016;42(5):316-27.

Ko SH, Ko SH, Ahn YB, Song KH, Han KD, Park YM, et al. Association of vitamin B12 deficiency and metformin use in patients with type 2 diabetes. J Korean Med Sci. 2014;29(7):965-72.

Liu Q, Li S, Quan H, Li J. Vitamin B12 status in metformin treated patients: Systematic review. PLoS One. 2014;9(6):e100379.

Kos E, Liszek M, Emanuele M, Durazo-Arvizu R, Camacho P. Effect of metformin therapy on vitamin D and vitamin B12 levels in patients with type 2 diabetes mellitus. Endocrine Practice. 2011;18(2):179-84.

Hoogeveen EK, Kostense PJ, Jakobs C, Bouter LM, Heine RJ, Stehouwer CD. Does metformin increase the serum total homocysteine level in non-insulindependent diabetes mellitus?. J Inter Med. 1997;242(5):389-94.

DeJager J, Kooy A, Lehert P, Wulffele MG, DerKolk JV, Bets D, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of Vitamin B12 de ciency: Randomised placebo controlled trial. BMJ. 2010;340:c2181.

Greibe E, Miller JW, Foutouhi SH, Green R, Nexo E. Metformin increases liver accumulation of vitamin B12-an experimental study in rats. Biochimie. 2013;95:1062-5.