• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (47)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in this journal  Social Bookmarking   What's this?

Rose Zhao-Wei Ting, MBBS; Cheuk Chun Szeto, MD, FRCP; Michael Ho-Ming Chan, FRCPA, FHKCPath; Kwok Kuen Ma, MBBS; Kai Ming Chow, MRCP

Arch Intern Med. 2006;166:1975-1979.

Background  Identification of risk factors for metformin-related vitamin B₁₂ deficiency has major potential implications regarding the management of diabetes mellitus.

Methods  We conducted a nested case-control study from a database in which the source population consisted of subjects who had levels of both serum vitamin B₁₂ and hemoglobin A_1c checked in a central laboratory. We identified 155 cases of diabetes mellitus and vitamin B₁₂ deficiency secondary to metformin treatment. Another 310 controls were selected from the cohort who did not have vitamin B₁₂ deficiency while taking metformin.

Results  A total of 155 patients with metformin-related vitamin B₁₂ deficiency (mean ± SD serum vitamin B₁₂ concentration, 148.6 ± 40.4 pg/mL [110 ± 30 pmol/L]) were compared with 310 matched controls (466.1 ± 330.4 pg/mL [344 ± 244 pmol/L]). After adjusting for confounders, we found clinically important and statistically significant association of vitamin B₁₂ deficiency with dose and duration of metformin use. Each 1-g/d metformin dose increment conferred an odds ratio of 2.88 (95% confidence interval, 2.15-3.87) for developing vitamin B₁₂ deficiency (P<.001). Among those using metformin for 3 years or more, the adjusted odds ratio was 2.39 (95% confidence interval, 1.46-3.91) (P = .001) compared with those receiving metformin for less than 3 years. After exclusion of 113 subjects with borderline vitamin B₁₂ concentration, dose of metformin remained the strongest independent predictor of vitamin B₁₂ deficiency.

Conclusions  Our results indicate an increased risk of vitamin B₁₂ deficiency associated with current dose and duration of metformin use despite adjustment for many potential confounders. The risk factors identified have implications for planning screening or prevention strategies in metformin-treated patients.

Author Affiliations: Departments of Medicine and Therapeutics (Drs Ting, Szeto, and Chow) and Chemical Pathology (Dr Chan), Prince of Wales Hospital, The Chinese University of Hong Kong, Sha Tin; and Department of Surgery, Queen Mary Hospital (Dr Ma), Hong Kong, China.

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

The Long and Short of Metformin-Related Vitamin B₁₂ Deficiency
George I. Varughese, Abd A. Tahrani, and John H. B. Scarpello
Arch Intern Med. 2007;167(7):729-730.
EXTRACT | FULL TEXT  

Metformin and Vitamin B₁₂ Deficiency: Association and Not Causation May Play a Major Role in Cohort Studies
Ishay Lev
Arch Intern Med. 2007;167(7):730.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Association of Biochemical B12 Deficiency With Metformin Therapy and Vitamin B12 Supplements: The National Health and Nutrition Examination Survey, 1999-2006
Reinstatler et al.
Diabetes Care 2012;35:327-333.
ABSTRACT | FULL TEXT  

Effects of Metformin on Body Weight and Body Composition in Obese Insulin-Resistant Children: A Randomized Clinical Trial
Yanovski et al.
Diabetes 2011;60:477-485.
ABSTRACT | FULL TEXT  

Review: Role of metformin in the management of polycystic ovary syndrome
Lashen
Therapeutic Advances in Endocrinology and Metabolism 2010;1:117-128.
ABSTRACT  

Reduced serum vitamin B-12 in patients taking metformin
Vidal-Alaball and Butler
BMJ 2010;340:c2198-c2198.
FULL TEXT  

Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial
de Jager et al.
BMJ 2010;340:c2181-c2181.
ABSTRACT | FULL TEXT  

Diabetes Medications Related to an Increased Risk of Falls and Fall-Related Morbidity in the Elderly
Berlie and Garwood
The Annals of Pharmacotherapy 2010;44:712-717.
ABSTRACT | FULL TEXT  

After Cardiac Surgery, How Does Nutrition Fit in With Risk Factors?
Kones
JPEN J Parenter Enteral Nutr 2010;34:163-168.
FULL TEXT  

Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome
Diamanti-Kandarakis et al.
Eur J Endocrinol 2010;162:193-212.
ABSTRACT | FULL TEXT  

Metformin Extended Release Treatment of Adolescent Obesity: A 48-Week Randomized, Double-Blind, Placebo-Controlled Trial With 48-Week Follow-up
Glaser Pediatric Research Network Obesity Study Gr
Arch Pediatr Adolesc Med 2010;164:116-123.
ABSTRACT | FULL TEXT  

Metformin, B12, and Enhanced Breast Cancer Response to Chemotherapy
Garcia and Tisman
JCO 2010;28:e19-e19.
FULL TEXT  

Reply to A. Garcia et al
Jiralerspong and Gonzalez-Angulo
JCO 2010;28:e20-e20.
FULL TEXT  

Association of Metformin, Elevated Homocysteine, and Methylmalonic Acid Levels and Clinically Worsened Diabetic Peripheral Neuropathy
Wile and Toth
Diabetes Care 2010;33:156-161.
ABSTRACT | FULL TEXT  

The Prevalence of Vitamin B12 Deficiency in Patients with Type 2 Diabetes: A Cross-Sectional Study
Pflipsen et al.
J Am Board Fam Med 2009;22:528-534.
ABSTRACT | FULL TEXT  

Longitudinal study of Chinese patients with pernicious anaemia
Chan et al.
Postgrad. Med. J. 2008;84:644-650.
ABSTRACT | FULL TEXT  

Vitamin B12 Deficiency in Patients Receiving Metformin: Clinical Data
Andres and Federici
Arch Intern Med 2007;167:729-729.
FULL TEXT  

Metformin and Vitamin B12 Deficiency: Association and Not Causation May Play a Major Role in Cohort Studies
Lev
Arch Intern Med 2007;167:730-730.
FULL TEXT  

The Long and Short of Metformin-Related Vitamin B12 Deficiency
Varughese et al.
Arch Intern Med 2007;167:729-730.
FULL TEXT  

Metformin-Induced Vitamin B12 Deficiency
JWatch Neurology 2007;2007:3-3.
FULL TEXT  

Endocrinology & Metabolism News November 2006
J. Clin. Endocrinol. Metab. 2006;91:17a-17a.
FULL TEXT