In reply: Metformin for type 2 diabetes

In Reply: We thank Dr. Moskowitz for his kind comments. We agree about the need for assessing vitamin B ₁₂ 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 B ₁₂ 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 B ₁₂ 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 B ₁₂ 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 B ₁₂-intrinsic factor complex. ³

Our electronic medical record has a built-in tool that suggests checking vitamin B ₁₂ whenever a patient requests metformin refills. There are no current guidelines on the need for baseline testing of the vitamin B ₁₂ level. The American Diabetes Association recommends periodic measurement of vitamin B ₁₂ levels, possibly yearly, in metformin users and more often if there are symptoms indicative of deficiency. ⁴