B12 deficiency may cause anemia, nerve damage (neuropathy), and dementia, among other problems.
Metformin is the cornerstone of drug therapy for type 2 diabetes. One reason is that it’s associated with improved cardiovascular disease outcomes—a claim few diabetic drugs can make. Prior studies established that metformin interferes with B12 absorption. The study at hand indicates that such malabsorption can reach a clinically significant degree, and that the falling blood levels are progressive over time.
Three diabetes clinic in the Netherlands provided 390 patients with type 2 diabetes between the ages of 30 and 80. They were all treated with 1) insulin and metformin 850 mg three times daily, or 2) insulin and placebo three times daily. B12 levels were drawn periodically over the course of the 4-year study. Seventy-two percent of participants completed the study (the drop-outs included 30 on metformin and 16 on placebo).
What Did the Investigators Find After Four Years?
- Compared with the placebo group, B12 levels in the metformin group dropped an average of 19%.
- Compared to the placebo group, the metformin cohort had a 7% risk of developing B12 deficiency (blood level under 150 pmol/l) and 11% risk of dropping into the “low B12” category (level 150-220 pmol/l).
It’s unclear whether these findings apply to diabetics not taking insulin or to other ethnicities and nationalities. I suspect they do.
The risk of developing B12 deficiency with metformin is not huge, but it seems to be real. Once B12 deficiency does it’s damage, it may not be totally reversible. So it’s important to know about this issue if you take or prescribe metformin. At this point I wouldn’t depend on my doctor to be aware of this adverse drug effect, nor to remember to check B12 levels periodically.
The researchers recommend that B12 levels be checked “regularly” in patients taking metformin, without defining a time frame. I suggest every year or two—closer to yearly if the patient has other risk factors for B12 deficiency, such as malnutrition, advanced age, removal of part of the stomach, some weight-loss surgeries, vegan diet, celiac disease, and Crohn’s disease.
de Jager, J., Kooy, A., Lehert, P., Wulffele, M., van der Kolk, J., Bets, D., Verburg, J., Donker, A., & Stehouwer, C. (2010). Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial BMJ, 340 (may19 4) DOI: 10.1136/bmj.c2181