Metformin and Vitamin B12 Deficiency: A Prevalence Study

Guidelines recommend routine biochemical screening for vitamin B12 deficiency in metformin users. However, these recommendations are based on non-specific and outdated definitions of vitamin B12 deficiency. Using contemporary diagnostic criteria, we compared prevalence in metformin users with non-users.

In this cross-sectional study, we included adults with diabetes (type 1, 2, other types) attending 2 outpatient clinics in Denmark, March 2024 to October 2025. Exposure was current use of metformin. B12 deficiency was defined by plasma B12 ≤ 250 pmol/L and elevated serum methylmalonic acid. Crude and adjusted prevalence differences (aPDs) and ratios (aPRs) were estimated using binomial regression.

Among 3958 participants (median age 54 years, 57% male) prevalence of vitamin B12 deficiency was 2.3% in current users and 1.3% in non-users (aPD of 0.7% [95% confidence interval [CI]: -0.32 to 1.7]; aPR of 1.56 [95% CI: 0.92 to 2.63]). In patients with type 2 diabetes (n = 1,338, median age 62 years, 61% male) prevalence was 2.3% versus 2.0% (aPD of 0.38% [95% CI: -1.9 to 1.1]; aPR of 1.21 [95% CI: 0.55 to 2.66]).

Vitamin B12 deficiency was uncommon with no meaningful excess risk among metformin users. Thus, routine screening may be redundant.