Associations between long-term metformin use, the risk of vitamin B12 deficiency, and neuropathy: An All of Us research Program study
Authors' conclusion
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.
Study context
- Population
- Adults with T2D in NIH's All of Us database9,136 metformin users
- Participants
- 14,808 adults
- Exposure
- Long-term metformin use vs short-term use vs no metformin
- Long-term usersn = 5,609
- Outcome
- Vitamin B12 deficiency and peripheral neuropathy
Methodological detailsobservational, unadjusted and adjusted logistic regression
- Observational
- Unadjusted and adjusted logistic regression
Main finding
As reported in the abstract
Vitamin B12 deficiency, long-term users vs non-users (adjusted): higher likelihood
67 %
p < 0.001
Vitamin B12 deficiency, long-term users vs short-term users (adjusted): higher likelihood
38 %
p < 0.001
Peripheral neuropathy prevalence, long-term vs short-term users: higher
39 %
p < 0.001
Observational data: associations, not effects.
Original publication
Associations between long-term metformin use, the risk of vitamin B12 deficiency, and neuropathy: An All of Us research Program study. Diabetes Res Clin Pract. Published 22 August 2025. doi:10.
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