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J Intern Med. 1997 Nov;242(5):389-94.

Does metformin increase the serum total homocysteine level in non-insulin-dependent diabetes mellitus?

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1
Institute for Research in Extramural Medicine, Vrije Universiteit, Amsterdam, The Netherlands. ellm.hoegeveen@paradigm.nl

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.

DESIGN:

A cross-sectional study in a primary care setting.

SUBJECTS, MAIN OUTCOME MEASURES:

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.

CONCLUSION:

We conclude that the effect of metformin on serum total homocysteine level in NIDDM patients, if any, is likely to be small.

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