Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial
Article first published online: 9 OCT 2003
Journal of Internal Medicine
Volume 254, Issue 5, pages 455–463, November 2003
How to Cite
Wulffelé, M. G., Kooy, A., Lehert, P., Bets, D., Ogterop, J. C., Borger van der Burg, B., Donker, A. J. M. and Stehouwer, C. D. A. (2003), Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. Journal of Internal Medicine, 254: 455–463. doi: 10.1046/j.1365-2796.2003.01213.x
- Issue published online: 9 OCT 2003
- Article first published online: 9 OCT 2003
- Received 13 January 2003; revision received 16 April 2003; accepted 7 May 2003.
- vitamin B12
Abstract. Wulffelé MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, Donker AJM, Stehouwer CDA (Bethesda General Hospital, Hoogeveen, The Netherlands; University of Mons, Mons, Belgium; Merck Nederland B.V., Amsterdam; Deaconesses’ Hospital, Meppel; Aleida Kramer Hospital, Coevorden; and Vrije Universiteit Medical Centre, Amsterdam; The Netherlands). Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med 2003; 254: 455–463.
Objective. Metformin is a key treatment option in type 2 diabetes. However, metformin may decrease vitamin B12 levels and increase levels of homo-cysteine, a cardiovascular risk factor. We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homo-cysteine, folate and vitamin B12 in subjects with type 2 diabetes treated with insulin.
Design. Placebo-controlled, randomized trial. Measurements: at baseline and 16 weeks later.
Setting. This trial was conducted in the outpatient clinics of three general hospitals in The Netherlands.
Subjects. A total of 745 patients with type 2 diabetes, treated with insulin and not known with a contraindication for the use of metformin, were approached; 390 gave informed consent and entered the study. Thirty-seven subjects dropped out (12 placebo and 25 metformin users).
Intervention. Addition of metformin or placebo to insulin therapy.
Primary outcome parameters. Serum homocysteine, folate, vitamin B12, indices of glycaemic control and body weight.
Results. Amongst those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with an increase in homocysteine of 4% (0.2 to 8; P = 0.039) and with decreases in folate [−7% (−1.4 to −13); P = 0.024] and vitamin B12 [−14% (−4.2 to −24); P < 0.0001]. In addition, the increase in homocysteine could be explained by the decreases in folate and vitamin B12.
Conclusion. In patients with type 2 diabetes, 16 weeks of treatment with metformin reduces levels of folate and vitamin B12, which results in a modest increase in homocysteine. The clinical significance of these findings remains to be investigated.