• Thu. Jan 20th, 2022

Metformin and Vitamin B12 Deficiency

The mechanism for for-4 low b12 and met with metformin I don’t think it’s been completely sorted out but it appears to be problem with absorption it’s not related to intrinsic factors so the classic pernicious anemia that we all learned about in medical school that’s not really the mechanism but there seems to be something about the effective metformin in the gut that impairs absorption so we studied much b12 levels in our metformin treated participants at two time points during DPP unfortunately we didn’t have samples available at the very beginning but we ere able to measure samples after  people had been treated for roughly five years and then again after nine years of treatment and we found that there was a significant prevalence of biochemical b12 deficiency that was higher in the metformin treatment participants than in the placebo group.

It was approximately depends on how you define b12 deficiency which is sort of a issuing – unto itself but people who had definitely low b12 was approximately 5% after five years of treatment and went up to about nine percent after longer longer duration treatment so what should we do clinically at this point well given what we know so far about the relationship between metformin and b12 deficiency I think there is some debate about whether everyone should be true everyone taking metformin should be treated there’s jokes about oh we should just add the 12 to the metformin tablet to take care of this problem I don’t think we’re quite there yet I think in part because we don’t even know what the the appropriate repletion method would be so we identify people ho have low b12 they’re taking metformin we think it’s likely that oral supplementation will be adequate but that really hasn’t been studied in any detail.

So I think being aware of the possibility of of low b12 is important that patients who are being treated with metformin and you know a DA a guidelines came out this year for the first time recommending periodic testing of b12 levels one thing I will mention about our findings in DPP that’s that’s relevant to the issue about how we deal with this clinically is that from the beginning of of the DPP study we were aware of the relationship between metformin and low b12 and so we were monitoring CBC’s during the study but we found in our analysis of the b12 levels that the the presence of Annie Mae did not discriminate between who did or didn’t have low b12 levels so I think we may have a false sense of security by looking by just analyzing hemoglobin and hematocrit for example in our metformin treated patients and I think that’s one of the reasons why guidelines there’s now starting to come out recommending actual measurement of vitamin b12 I think it’s hard at this point to have a precise recommendation for when to begin measuring but I think within a few years of starting metformin is probably when I would start to consider doing it so the question clinically is whether we should be treating all patients who are taking metformin with a vitamin b12 supplement or whether we should be testing them what’s the most cost effective approach I think that one could make an argument for providing b12 supplement to everyone who is taking metformin but the one caveat to that is that I don’t think that the appropriate treatment regimen has really been clearly identified we we believe we expect that higher doses of vitamin b12 will overcome the malabsorption that’s associated with metformin but we don’t know that for sure and I think it would be somewhat risky to recommend routine supplementation with without some measurement of vitamin b12 levels.

At some point just to assure that if there was malabsorption that had been overcome the question can come up whether the risk of vitamin b12 deficiency might be  factor in decision to actually  prescribe metaphor man should this be a reason to avoid prescribing that Foreman especially in these days when there are many other oral medications or easily administered medications that we could choose from and my personal view is that that’s probably not warranted there’s so many benefits to metformin as such an excellent safety profile and inexpensive readily affordable readily available drug that I think that it can be safely prescribed as long as the potential for b12 deficiency is is recognized.