Review Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency Elias E. Mazokopakis a, *, Ioannis K. Starakis b a Department of Internal Medicine, Naval Hospital of Crete, 73 200 Chania, Crete, Greece b Department of Internal Medicine, Patras University Hospital, 26 500 Rion-Patras, Greece Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360 2. Prevalence and pathogenesis of MICD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360 3. Diagnosis of MICD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361 3.1. Measurement of the serum Cbl and the red blood cell (or serum) folate concentrations . . . . . . . . . . . . . . . . . 361 3.2. Measurement of specific metabolic intermediates (tHcy, MMA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362 3.3. Evaluation of tests results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362 3.4. Exclusion other causes of Cbl deficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 4. Treatment and prevention of MICD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366 d i a b e t e s r e s e a r c h a n d c l i n i c a l p r a c t i c e 9 7 ( 2 0 1 2 ) 3 5 9 – 3 6 7 a r t i c l e i n f o Article history: Received 27 February 2012 Received in revised form 17 May 2012 Accepted 12 June 2012 Published on line 7 July 2012 Keywords: Cobalamin Deficiency Folate Homocysteine Metformin MMA Vitamin B12 a b s t r a c t Metformin treatment is a known pharmacological cause of vitamin B12 (Cbl) deficiency with controversial responsible mechanisms. A possible diagnosis of this deficiency is based mainly on the combination of patient’s medical history (usually long-term metformin use), clinical examination (possible neuropsychiatric symptoms and signs), laboratory studies which confirm a Cbl deficiency (haematological abnormalities, low serum Cbl levels, elevated serum total homocysteine and methylmalonic acid levels), and exclusion other causes of Cbl deficiency (as pernicious anaemia, food-cobalamin malabsorption syndrome, other drugs, etc.). In our review, recommendations for diagnosis and management of metformin-induced Cbl deficiency (MICD) in diabetic patients based on medical bibliogra- phy are presented and discussed. # 2012 Elsevier Ireland Ltd. All rights reserved. * Corresponding author at: Iroon Polytechniu 38A, Chania 73 132, Crete, Greece. Tel.: +30 2821 082754; fax: +30 2821 082510. E-mail address: emazokopakis@yahoo.gr (E.E. Mazokopakis). Contents available at Sciverse ScienceDirect Diabetes Research and Clinical Practice journal homepage: www.elsevier.com/locate/diabres 0168-8227/$ – see front matter # 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.diabres.2012.06.001