Prevalence of Vitamin B12 Deficiency in Patients Treated With Metformin
Abstract
Background/aim: Metformin has been associated with vitamin B12 (cobalamin) deficiency, pushing scientific societies such as the American Diabetes Association and the European Association for the Study of Diabetes to emphasise the need for screening B12 levels, without specific metformin doses or exposure durations triggering this screening. Robust data regarding the prevalence of B12 deficiency in metformin-treated patients in Portugal are currently lacking. Aim of this study was to identify the prevalence of B12 deficiency in a sample of diabetic patients taking metformin. Secondary objectives were determining the minimum dose and minimum and median time exposure time leading to this deficiency and identifying the average duration of metformin use in the patients with this deficiency.
Methods: Descriptive and cross-sectional observational study was performed on a sample of 79 users from a population of 714 diabetic patients on metformin. Inclusion criteria comprised individuals aged 18 or older, receiving metformin for at least 1 month and voluntarily participating in the study. Exclusion criteria included a history of gastrectomy or B12 supplementation.
Results: A prevalence of 25.3 % of vitamin B12 deficiency was identified in the study sample. Minimum doses of 500 mg of metformin per day and a minimum exposure period of 1 year were associated with B12 deficiency. An average exposure time of 5.33 years was identified.
Conclusion: These results align with the prevalence described in the few international studies and should alert physicians to potential clinical manifestations of this deficiency, such as anaemia and neurological symptoms like neuropathy.
References
Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 2019;157:107843. doi: 10.1016/j.diabres.2019.107843.
Drzewoski J, Hanefeld M. The current and potential therapeutic use of metformin-the good old drug. Pharmaceuticals (Basel). 2021 Feb 5;14(2):122. doi: 10.3390/ph14020122.
American Diabetes Association. Standards of medical care in diabetes-2020 abridged for primary care providers. Clin Diabetes. 2020 Jan;38(1):10-38. doi: 10.2337/cd20-as01.
Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, et al. Management of hyperglycemia in type 2 diabetes, 2018. a consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-701. doi: 10.2337/dci18-0033.
LeRoith D, Biessels GJ, Braithwaite SS, Casanueva FF, Draznin B, Halter JB, et al. Treatment of diabetes in older adults: an endocrine society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019 May 1;104(5):1520-74. doi: 10.1210/jc.2019-00198.
Diabetes Canada Clinical Practice Guidelines Expert Committee; Lipscombe L, Booth G, Butalia S, Dasgupta K, Eurich DT, Goldenberg R, et al. Pharmacologic glycemic management of type 2 diabetes in adults. Can J Diabetes. 2018 Apr;42 Suppl 1:S88-S103. doi: 10.1016/j.jcjd.2017.10.034.
Yang W, Cai X, Wu H, Ji L. Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis. J Diabetes. 2019 Sep;11(9):729-43. doi: 10.1111/1753-0407.12900.
Roy RP, Ghosh K, Ghosh M, Acharyya A, Bhattacharya A, Pal 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):631-7. doi: 10.4103/2230-8210.190542.
Stabler SP, Allen RH, Savage DG, Lindenbaum J. Clinical spectrum and diagnosis of cobalamin deficiency. Blood. 1990 Sep 1;76(5):871-81. PMID: 2393714.
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 Nov;98(46):e17918. doi: 10.1097/MD.0000000000017918.
Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ et al. Diabetes Prevention Program Research Group. 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.
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.
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 Jul;29(7):965-72. doi: 10.3346/jkms.2014.29.7.965.
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.
Larry E. Johnson. Vitamin B12 Deficiency. MSD Manual Professional Version. 2024.[Internet]. [Cited: 24-Feb-2024]. Available at: https://www.msdmanuals.com/professional/nutritional-disorders/vitamin-deficiency,-dependency,-and-toxicity/vitamin-b12-deficiency?query=Vitamin%20B12%20Deficiency.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).