NutriStack
Metformin and Vitamin B12, a caution.
Long-term metformin use (typically >6 months) reduces vitamin B12 absorption by 10-30%, leading to deficiency in up to 30% of chronic users. B12 deficiency from metformin can cause peripheral neuropathy that may be misattributed to diabetic neuropathy, and megaloblastic anemia.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Metformin and Vitamin B12
- Pair type
- Caution
- Evidence (highest tier)
- Strong
- Source citations
- 3 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Strong evidence
Caution
What is happening. Long-term metformin use (typically >6 months) reduces vitamin B12 absorption by 10-30%, leading to deficiency in up to 30% of chronic users. B12 deficiency from metformin can cause peripheral neuropathy that may be misattributed to diabetic neuropathy, and megaloblastic anemia.
Mechanism. Metformin interferes with calcium-dependent binding of the intrinsic factor-B12 complex to the ileal receptor (cubilin). Since B12 absorption in the terminal ileum requires calcium-dependent endocytosis, metformin's disruption of this process reduces B12 uptake.
Recommendation. Monitor B12 levels annually if on long-term metformin. Consider B12 supplementation (1000 mcg/day sublingual or 1000 mcg/month injection) as prophylaxis, particularly in patients on metformin for over 1 year.
Sources (3)
- Aroda VR et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-1761. PMID 26900641
- de Jager J et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency. BMJ. 2010;340:c2181. PMID 20488910
- Maruthur NM, Tseng E, Hutfless S, Wilson LM et al.. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Annals of Internal Medicine. 2016. PMID 27088241
Stack Score
How this pair moves the number.
Effect on the composite score
If both Metformin and Vitamin B12 are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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