Long-Term Metformin May Lead to Vitamin B12 Deficiency

Metformin is the most prescribed drug for people with type 2 diabetes.  It’s one of the few anti-diabetic drugs that has been shown to reduce cardiovascular disease and mortality.  It’s known that metformin interferes with the absorption of vitamin B12, but no long-term studies of this effect have been published – until now.  The British Medical Journal contains a report of 4-year treatment of type 2 diabetics with metformin, in comparison to placebo.

Outpatient clinics in the Netherlands provided 390 type 2 patients receiving insulin.   They were given 850 mg metformin or placebo three times a day, for an average of 4.3 years.  Changes in vitamin B12, folate, and homocysteine levels were measured at 4, 17, 30, 43, and 52 months.

The patients who were given metformin were found to have a 19% reduction in their vitamin B12 levels, compared with the placebo patients, who had virtually no change in their levels over the whole study period.  The changes with the metformin group, however, got more pronounced over time.  The numbers of those at the ‘deficiency level’ (below 150 pmol/L) increased from 3 at enrollment to 19 at study end, compared with 4 to 5 for the placebo group.  The metformin-treated patients also had a 5% increase in homocysteine, but the folate levels were unaffected.

The progressive nature of the metformin effect is troubling.  The authors of the study state: “Our study shows that it is reasonable to assume harm will eventually occur in some patients with metformin-induced low vitamin B12 levels.”  They go on to suggest that blood levels of vitamin B12 should be monitored regularly in patients taking metformin.  An editorialist in the same issue of the BMJ, however, thinks one should first see whether simple dietary counseling when metformin is started should be a first step.  If diet counseling doesn’t work, vitamin B12 monitoring may be necessary.  In the meantime, diabetics taking metformin shouldn’t panic.  Their family doctor and their diabetes specialist will be aware of the slight risk of B12 reductions, and will test blood levels, if necessary.