The vitamin B12 levels in type 2 diabetes mellitus patients on metformin and not on metformin

Authors

  • Ramesh Dasarathan Department of Medicine, Madras Medical College, Chennai, Tamil Nadu, India
  • Rajendran Velayudham Department of Medicine, Madras Medical College, Chennai, Tamil Nadu, India
  • Haridoss Krishnan Department of Medicine, Madras Medical College, Chennai, Tamil Nadu, India
  • Senthilkumar S. Department of Medicine, Madras Medical College, Chennai, Tamil Nadu, India

DOI:

https://doi.org/10.18203/2349-3933.ijam20210270

Keywords:

Type 2 diabetes mellitus, Metformin, Vitamin B12 deficiency

Abstract

Background: Type 2 diabetes mellitus (T2DM) is one of the major global public health concerns, metformin is one of the most widely used drugs and considered as first-line therapy for management of T2DM. Vitamin B12 malabsorption is observed in patients on metformin therapy leading to biochemical and clinical vitamin B12 deficiency. The aim of the current study was to assess the relationship between metformin therapy and development of vitamin B12 deficiency.

Methods: Current observational cross sectional study was conducted at Madras medical college and Rajiv Gandhi Government general hospital. Serum vitamin B12 and other blood investigation parameters of T2DM patients, on metformin therapy for long duration (6 months or more than 2 years) were measured and correlated with vitamin B12 levels of T2DM patients not on metformin therapy. Patients were given appropriate treatment and were regularly followed up.

Results: Results of the current study findings depicted that significant difference was observed in percent haemoglobin, total blood cells, platelet count, mean corpuscular volume (MCV) and albumin values of patients on metformin therapy when compared to patients who were not on metformin therapy. Study findings also revealed that substantial difference in vitamin B12 deficiency was observed in T2DM patients based on the duration of metformin therapy.

Conclusions: Current study revealed that, metformin therapy for 2 years or more, can lead to significant vitamin B12 deficiency which is also associated with macrocytosis. It was concluded that longer the duration of metformin therapy, more significant would be vitamin B12 deficiency.

References

Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88-98.

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. Diabetes Res Clin Pract. 2019;157:107843.

Cho NH, Shaw JE, Karuranga S. Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271-81.

Abraham TM, Pencina KM, Pencina MJ, Fox CS. Trends in diabetes incidence: the Framingham Heart Study. Diabetes Care. 2015;38:482-7.

Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends. J Epidemiol Glob Health. 2020;10(1):107-11.

Nasri H, Rafieian-Kopaei M. Metformin: Current knowledge. J Res Med Sci. 2014;19(7):658-64.

Wang YW, He SJ, Feng X. Metformin: a review of its potential indications. Drug Des Devel Ther. 2017;11:2421-9.

Zilov AV, Abdelaziz SI, AlShammary A. Mechanisms of action of metformin with special reference to cardiovascular protection. Diabetes Metab Res Rev. 2019;35(7):e3173.

Zhou J, Massey S, Story D, Li L. Metformin: an old drug with new applications. Int J Mol Sci. 2018;19(10):2863.

Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017;60(9):1577-85.

Sanchez-Rangel E, Inzucchi SE. Metformin: clinical use in type 2 diabetes. Diabetologia. 2017;60(9):1586-93.

Graham GG, Punt J, Arora M. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 2011;50:81-98.

Scott J.M. Bioavailability of vitamin B12. Eur J Clin Nutr. 1997;51:49-53.

O'Leary F, Samman S. Vitamin B12 in health and disease. Nutrients. 2010;2(3):299-316.

Al-Hamdi A, Al-Gahhafi M, Al-Roshdi S, Jaju S, Al-Mamari A, Al Mahrezi AM. Vitamin B12 Deficiency in Diabetic Patients on Metformin Therapy: A cross-sectional study from Oman. Sultan Qaboos Univ Med J. 2020;20(1):90-4.

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;29:965-72.

Wong CW, Leung CS, Leung CP, Cheng JN. Association of metformin use with vitamin B12 deficiency in the institutionalized elderly. Arch Gerontol Geriatr. 2018;79:57-62.

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;42:316-27.

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;11:729-43.

Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ, et al. Long-term metformin use and vitamin B12 deficiency in the diabetes prevention program outcomes study. J Clin Endocrinol Metab. 2016;101:1754-61.

Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP. Association of biochemical B12 deficiency with metformin therapy and vitamin B12 supplements: The national health and nutrition examination survey, 1999–2006. Diabetes Care. 2012;35:327-33.

de Jager J, Kooy A, Lehert P, Wulffelé MG, van der Kolk J, Bets D, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: Randomised placebo controlled trial. BMJ. 2010;340:2181.

Hendrawati YD, Andrajati R, Supardi S, Ariyani A. The risk of cobalamin deficiency symptoms related to long-term metformin use in T2DM patients. Acta Endocrinol. 2018;14:49-54.

Berchtold P, Bolli P, Arbenz U, Keiser G. Disturbance of intestinal absorption following metformin therapy. Diabetologia. 1969;5:405-12.

Tomkin GH, Hadden DR, Weaver JA, Montgomery DA. Vitamin-B12 status of patients on long-term metformin therapy. Br Med J. 1971;2:685-7.

Pflipsen MC, Oh RC, Saguil A, Seehusen DA, Seaquist D, Topolski R. The prevalence of vitamin B(12) deficiency in patients with type 2 diabetes: a cross-sectional study. J Am Board Fam Med. 2009;22(5):528-34.

Shobha V, Tarey SD, Singh RG. Vitamin B₁₂ deficiency & levels of metabolites in an apparently normal urban south Indian elderly population. Indian J Med Res. 2011;134(4):432-9.

Downloads

Published

2021-01-27

Issue

Section

Original Research Articles