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

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 B-12, 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 mu mol 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 mu mol L-1 in the metformin-exposed patients and 10.6 mu mol L-1 in the nonexposed patients. Thus, the metformin-exposed patients had slightly higher serum total homocysteine levels (difference 0.8 mu mol L-1, 95% confidence interval (-0.4-2.0 mu mol 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.