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.