title: Vitamin B12 status in metformin treated patients: systematic review.
abstract: OBJECTIVE
  Randomized controlled trials and observational studies have yielded inconsistent results on the effects of metformin on vitamin B12 reduction. We therefore performed a systematic review to analyze the effects of metformin on vitamin B12 concentration.
  
  
  METHODS
  PubMed, Medline, Embase, and the Cochrane central registry of controlled trials were searched to identify randomized controlled trials and observational studies exploring the association between metformin and vitamin B12 concentration in patients with type 2 diabetes mellitus or polycystic ovary syndrome. The main outcome measure was changes in serum vitamin B12 concentration after 6-208 weeks of treatment with metformin, as compared with placebo or other anti-hyperglycemic therapy.
  
  
  RESULTS
  Six randomized controlled trials met the inclusion criteria. Serum vitamin B12 concentrations were significantly lower in patients treated with metformin than in those who received placebo or rosiglitazone (mean difference [MD], -53.93 pmol/L; 95% confidence interval [CI], -81.44 to -26.42 pmol/L, P = 0.0001). Subgroup analysis identified four trials in which patients received a lower dose of metformin (<2000 mg/d) and two in which they received a higher dose (≥2000 mg/d), with MDs in vitamin B12 concentration after metformin treatment of -37.99 pmol/L (95% CI, -57.44 to -18.54 pmol/L, P = 0.0001) and -78.62 pmol/L (95% CI, -106.37 to -50.86 pmol/L, P<0.00001), respectively.
  
  
  CONCLUSIONS
  The reduction of vitamin B12 may be induced by metformin in a dose dependent manner.
authors: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
authors: Qilin
authors: Q
authors: Liu
authors: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
authors: Sheyu
authors: S
authors: Li
authors: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
authors: Heng
authors: H
authors: Quan
authors: Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China.
authors: Jianwei
authors: J
authors: Li
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin; D014805:Vitamin B 12