Departments

In reply: Metformin for type 2 diabetes January 2019

Vinni Makin, MBBS, MD, FACE and M. Cecilia Lansang, MD, MPH
Cleveland Clinic Journal of Medicine April 2019, 86 (4) 237; DOI: https://doi.org/10.3949/ccjm.86c.04004

We thank Dr. Moskowitz for his kind comments. We agree about the need for assessing vitamin B12 levels during chronic metformin use.

Secondary analysis of patients in the Diabetes Prevention Program Outcomes Study showed a higher incidence of combined low and low-normal vitamin B12 deficiency in users assigned to the metformin group compared with those assigned to the placebo group at the 5-year and 13-year marks after randomization.1 Post hoc analysis of patients in the Hyperinsulinemia: the Outcome of Its Metabolic Effects trial also showed lower levels of vitamin B12 and higher levels of methylmalonic acid associated with significant worsening of a validated neuropathy score in metformin users.2

The mechanism behind the development of vitamin B12 deficiency is not completely understood but could possibly be alterations in intestinal mobility, bacterial overgrowth, or calcium-dependent uptake by ileal cells of the vitamin B12-intrinsic factor complex.3

Our electronic medical record has a built-in tool that suggests checking vitamin B12 whenever a patient requests metformin refills. There are no current guidelines on the need for baseline testing of the vitamin B12 level. The American Diabetes Association recommends periodic measurement of vitamin B12 levels, possibly yearly, in metformin users and more often if there are symptoms indicative of deficiency.4

REFERENCES

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    . 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2019. Diabetes Care 2019; 42(suppl 1):S90–S102. doi:10.2337/dc19-S009