title: Does metformin increase the serum total homocysteine level in non-insulin-dependent diabetes mellitus?
abstract: OBJECTIVE
  The aim of this study was to estimate the effect of metformin on the serum total homocysteine level in non-insulin-dependent diabetes mellitus (NIDDM) patients. An elevated serum total homocysteine level is a risk factor for atherosclerosis. Metformin decreases serum vitamin B12, and may thereby indirectly increase the serum total homocysteine level.
  
  
  METHODS
  A cross-sectional study in a primary care setting.
  
  
  METHODS
  Fasting serum total homocysteine level was measured in 40 NIDDM patients who had received treatment with metformin (500-2550 mg per day) for at least six months, and in 71 NIDDM patients not treated with metformin and matched for sex, age (+/- 5 years), serum creatinine (+/- 5 micromol L[-1]) and current smoking habits. 'Exposed' patients were matched with 'nonexposed' patients. A two-way analysis of variance was performed.
  
  
  RESULTS
  The mean serum total homocysteine level was 11.5 micromol L(-1) in the metformin-exposed patients and 10.6 micromol L(-1) in the nonexposed patients. Thus, the metformin-exposed patients had slightly higher serum total homocysteine levels (difference 0.8 micromol L(-1), 95% confidence interval (-0.4-2.0 micromol L[-1]). Results were similar in men and women. Finally, no dose-response relationship between cumulative exposure to metformin (dose x duration of treatment) and the serum total homocysteine level could be demonstrated.
  
  
  CONCLUSIONS
  We conclude that the effect of metformin on serum total homocysteine level in NIDDM patients, if any, is likely to be small.
authors.affiliation: Institute for Research in Extramural Medicine, Vrije Universiteit, Amsterdam, The Netherlands. ellm.hoegeveen@paradigm.nl
authors.forename: E K
authors.initials: EK
authors.lastname: Hoogeveen
authors.forename: P J
authors.initials: PJ
authors.lastname: Kostense
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: L M
authors.initials: LM
authors.lastname: Bouter
authors.forename: R J
authors.initials: RJ
authors.lastname: Heine
authors.forename: C D
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000139:chemically induced; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006710:Homocysteine / Q000009:adverse effects / Q000097:blood* / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D006710:Homocysteine; D008687:Metformin