Associations between long-term metformin use, the risk of vitamin B12 deficiency, and neuropathy: An All of Us research Program study

Aims

The primary objective of this study is to investigate the associations between long-term metformin use, vitamin B12 status, and peripheral neuropathy. Secondarily, we aim to explore the effect of time since diagnosis on the relationships between metformin use, vitamin B12 deficiency, and peripheral neuropathy.

Methods

A retrospective observational cross-sectional analysis was conducted using NIH’s All of Us database. The risk of vitamin B12 deficiency and peripheral neuropathy was compared among long-term metformin users (≥4 years), short-term users (<4 years), and non-metformin users via a series of unadjusted and adjusted logistic regression models.

Results

Among 14,808 adults with type 2 diabetes mellitus (T2DM), 9,136 (61.70 %) used metformin, of whom 5,609 (37.95 %) were long-term users. Following adjustment for confounders, long-term users exhibited a 67 % and 38 % higher likelihood of vitamin B12 deficiency than non-users and short-term users respectively (p < 0.001). Peripheral neuropathy prevalence was 39 % higher among long-term users compared to short-term users (p < 0.001), with a non-statistically significant difference compared to non-users.

Conclusions

Long-term metformin use is associated with both an increased risk of vitamin B12 deficiency and peripheral neuropathy in patients with T2DM. Providers should consider routinely assessing vitamin B12 status in long-term users, particularly when evaluating peripheral neuropathy symptoms.