Published: 2016-12-29

A comparative study of levels of vitamin B12 in patients of type 2 diabetes mellitus on metformin and not on metformin at tertiary care center

Priti Agarwal, Pradeep Mital, Vinay Kumar Meena, Premlata Mital, C. L. Nawal, Laxmi Kant Goyal


Background: Type 2 diabetes mellitus is associated with vitamin B12 deficiency which is further increased in patients who are on metformin therapy. The objective of this study is to determine the frequency of vitamin B12 deficiency among Indian patients with type 2 diabetes mellitus on metformin therapy compared to those who are not on metformin.

Methods: The study was a hospital based, case control type of analytical study conducted in SMS Medical College & Hospital, Jaipur during a period of 1 year. The study group has 50 patients with a diagnosis of T2DM and a prescription history of metformin for ≥18 months and control group has 50 patients with diagnosis of T2DM and no history of metformin use in the past five years. The following data was recorded for each patient: age, sex, weight, height, body mass index (BMI), years with diabetes, total daily dose of and years on metformin. Serum vitamin B12 was measured using an immunoassay method. Data were statistically analyzed.

Results: Mean serum vitamin B12 levels in the study group was 431.84±265.76 and in control was 744.76±271.927 and the difference was statistically significant. Mean serum vitamin B12 levels in vegetarians (547.27±303.011) were significantly lower than in non-vegetarian (699.22±307.992) (p value 0.029). A significant negative correlation existed between the S. vitamin B12 and duration of diabetes (r= -0.445) by using Pearson’s correlation coefficient in study group.

Conclusions: Metformin is significantly associated with decrease in vitamin B12. So we recommend that vitamin B12 should be measured prior to initiation of metformin therapy and later annually  in patients of type 2 diabetes mellitus who are on metformin therapy for long duration (≥3-4 years) or in higher doses (≥2gm/day).


Vitamin B12, Type 2 diabetes mellitus, Metformin

Full Text:



Joshi SR, Parikh RM. India - diabetes capital of the world: now heading towards hypertension. J Assoc Physicians India. 2007;55:323-4.

Kumar A, Goel MK, Jain RB, Khanna P, Chaudhary V. India towards diabetes control: Key issues. Australas Med J. 2013;6(10):524-31.

Marar O, Senturk S, Agha A, Thompson C, Smith D. The prevalence of vitamin B12 deficiency in patients with type 2 diabetes Mellitus on metformin. Royal College of Surgeons in Ireland Student Medical Journal. 2011;4(1):16-20.

Pflipsen MC, Oh RC, Saguil A, Seehusen DA, Topolski R. The prevelance of vitamin B12 deficiency in patients with type 2 diabetes: a cross sectional study. J Am Board Fam Med. 2009;22(5):528-34.

Albers U, Pedrero-Chamizo R, Melendez A, Pietrzik K, Castillo MJ, Gonzalez-Gross M. Efficacy of a 28-Day Oral Cyanocobalamin Supplementation on Vitamin B Status in Spanish Institutionalized Elderlyly. International Journal for Vitamin and Nutrition Research. 2012;82(2):104-12.

Gale EA, Gillespie KM. Diabetes and gender. Diabetologia. 2001;44(1):3-15.

Boffetta P, McLerran D, Chen Y, Inoue M, Sinha R, et al. Body mass index and diabetes in Asia: a cross-sectional pooled analysis of 900,000 individuals in the Asia cohort consortium. PLoS One. 2011;6: e19930.

Chan WB, Tong PC, Chow CC, So WY, Ng MC, et al. The associations of body mass index, C-peptide and metabolic status in Chinese Type 2 diabetic patients. Diabet Med. 2004;21:349-53.

Xu H, Song Y, You NC, Zhang ZF, Greenland S, et al. Prevalence and clustering of metabolic risk factors for type 2 diabetes among Chinese adults in Shanghai, China. BMC Public Health. 2010;10: 683.

Evans JMM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ volume. 2005;330:1304-05.

Yajnik C, Deshpande S, Lubree H. Vitamin B12 Deficiency and Hyperhomocysteinemia in Rural and Urban Indians. JAPI. 2006;54:775-82.

Mazokopakis EE, Starakis IK. Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency. Diabetes Research and Clinical Practice. 2012;97(3):359-67.

Reinstatler L, Qi, YP, Williamson RS, Garn JV, Oakley GP. Association of Biochemical B-12 Deficiency With metformin Therapy and Vitamin B-12 Supplements The National Health and Nutrition Examination Survey, 1999-2006. Diabetes Care. 2012;35(2), 327-33.

DeFronzo R, Goodman A. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med. 1995;333:541-9.

Hermann L, Nilsson B, Wettre S. Vitamin B12 status of patients treated with metformin: a cross-sectional cohort study. British Journal of Diabetes & Vascular Disease. 2004;4:401.

Nervo M, Lubini A, Raimundo F. Vitamin B12 in metformin-treated diabetic patients: a cross-sectional study in Brazil. Rev Assoc Med Bras. 2011;57:46-9.

Liu K, Dai L, Jean W. Metformin-related vitamin B12 deficiency. Age Ageing. 2006;35:200-1.

Bell D. Metformin-induced vitamin B12 deficiency presenting as a peripheral neuropathy. South Med J. 2010;103:265-7.

Kumthekar A, Gidwani H, Kumthekar A. Metformin Associated B12 Deficiency. Journal of the Association of Physicians of India. 2012;60:58-9.

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. Endocr Pract. 2012;18:179-84.

De-Jager J, Kooy A, Lehert P. 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:c2181.

Ting R, Szeto C, Chan M, Ma K, Chow K. Risk Factors of Vitamin B12 Deficiency in Patients Receiving Metformin. Arch Intern Med. 2006;166:1975-9.

Reinstatler L, Qi Y, Williamson R, Garn J, Oakley-Jr G. 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.

Green S, Watson R. Nutritional screening and Assessment Tools for older adults: Literature Review. Journal of Advance nursing. 2006;54(4):477-90.

McElnay C, Marshall B, O'Sullivan J, Jones L, Ashworth T, Hicks K, Forrest R. Nutritional risk amongst community-living Maori and non-Maori older people in Hawke's Bay. Journal of primary health care. 2012;4(4):299-305.

Graham GG, Punt J, Arora, M, Day RO, Doogue, MP, Duong JK, Williams KM. Clinical Pharmacokinetics of metformin. Clinical Pharmacokinetics. 2011;50(2):81-98.