Thread by @mendesthiagob

🤔 Does metformin cause vitB12 deficiency?

❗️Metformin is the most prescribed drug for type 2 diabetes. Should you monitor vit B12 in pts taking it?

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Let's start with a poll. Do you order vit B12 for pts taking metformin?

ADA Standards of Care 2022

"Long-term use of metformin may be associated with biochemical vitamin B12 deficiency; consider periodic measurement of vitamin B12 levels in metformin-treated patients, especially in those with anemia
or peripheral neuropathy."
pubmed.ncbi.nlm.nih.gov/34964876/

The statement above is level of evidence B (good), but what is the meaning of "may be associated" and "consider"?

Let's go to some evidence!

A study assessing 1,621 pts with type 2 diabetes from NHANES database showed the following for vitB12 deficiency:

- Taking metformin: 5.8%
- Not taking metformin: 2.4%
Adjusted OR: 2.92 (CI 95%: 1.26-6.78)

pubmed.ncbi.nlm.nih.gov/22179958/

Multiple studies confirmed the results above.

Metformin is associated with lower levels of serum vitB12, while most pts taking the drug have normal vit B12.

pubmed.ncbi.nlm.nih.gov/27130885/

But, are we assessing vitB12 in pts taking metformin?

In an outpatient setting in the US, only 25% of pts taking metformin had vitB12 measurement in a 5-year timeframe.

pubmed.ncbi.nlm.nih.gov/31592289/

Anyways, it is important to acknowledge that the ADA recommendation to screen vitB12 began in 2017. Did it impact practice?

This unicentric VA study showed that vitB12 screening in pts taking metformin increased from 2016 (34.5%) to 2018 (50.3%).

pubmed.ncbi.nlm.nih.gov/31955662/

Maybe we are now taking a deeper look at vitB12 in pts taking metformin. Can we improve their outcomes with this approach?

A meta-analysis didn't find an association btw metformin use and neuropathy or anemia, despiting confirming lower levels of vitB12 in those taking metformin.

pubmed.ncbi.nlm.nih.gov/30615306/

Time of follow-up (not so long) is a caveat in these studies.

DPP/DPPOS, the big trial designed to assess metformin for prediabetes, follow-up for 13 years:

Pts taking metformin and with low vit B12 had more neuropathy.

❗️From 898 pts that had taken metformin, only 56 had low vit B12, of which 13 had neuropathy.
pubmed.ncbi.nlm.nih.gov/26900641/

Another caveat is that serum levels of vit B12 are poor predictors of intracellular activity. Maybe we are not getting a good sense of vitB12 status by dosing it.

pubmed.ncbi.nlm.nih.gov/23168250/

Do you plan to order vitB12 for pts taking metformin from now on?

Please, feel free to add more evidence!