Component

Risk of biochemical vitamin B12 deficiency during metformin treatment

Risk of biochemical vitamin B12 deficiency during metformin treatment. Species, exposure and limitations are retained in each linked claim.

3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

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How nutrients influence it

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Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

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What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. The absolute risk of vitamin B-12 deficiency below 150 pmol/l was 7.2 percentage points higher in the metformin group, with a number needed to harm of 13.8 per 4.3 years.

    Metformin → Risk of biochemical vitamin B12 deficiency during metformin treatment source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/metformin-research/20488910.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c9e09d44fe1103e6927321e925e69e31c38d1a688fd2ac18ea96927098de922", "start_char": 0, "end_char": 2518, "text_sha256": "6c9e09d44fe1103e6927321e925e69e31c38d1a688fd2ac18ea96927098de922"}
    experimental_model
    Multicentre randomised placebo-controlled trial, 390 people with type 2 diabetes on insulin
    exposure
    850 mg metformin three times daily for 4.3 years versus placebo
    limitations
    The strongest available human causal evidence for the B12 effect. It measured concentrations and deficiency incidence, not clinical deficiency syndromes.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Human
    plain_language
    Roughly one in fourteen people treated for four years crossed into deficiency.
    primary_references
    [metformin-p20488910] Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. (2010). https://pubmed.ncbi.nlm.nih.gov/20488910/ DOI: 10.1136/bmj.c2181
    tissue_or_cell_type
    Whole body
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1048–1059

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicentre randomised placebo-controlled trial, 390 people with type 2 diabetes on insulin · source_derived_draft · unverified_draft

    ### metformin-b12-deficiency-risk The absolute risk of vitamin B-12 deficiency below 150 pmol/l was 7.2 percentage points higher in the metformin group, with a number needed to harm of 13.8 per 4.3 years. Condition category: nutrient_deficiency nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Roughly one in fourteen people treated for four years crossed into deficiency. organism: Human tissue_or_cell_type: Whole body experimental_model: Multicentre randomised placebo-controlled trial, 390 people with type 2 diabetes on insulin limitations: The strongest available human causal evidence for the B12 effect. It measured concentrations and deficiency incidence, not clinical deficiency syndromes. exposure: 850 mg metformin three times daily for 4.3 years versus placebo evidence_span: {"source_cache": "artifacts/metformin-research/20488910.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c9e09d44fe1103e6927321e925e69e31c38d1a688fd2ac18ea96927098de922", "start_char": 0, "end_char": 2518, "text_sha256": "6c9e09d44fe1103e6927321e925e69e31c38d1a688fd2ac18ea96927098de922"} [metformin-p20488910] Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. (2010). https://pubmed.ncbi.nlm.nih.gov/20488910/ DOI: 10.1136/bmj.c2181
    Complete structured claim and evidence

  2. Each 1 g/day increment in metformin dose conferred an odds ratio of 2.88 for vitamin B12 deficiency, and use for three years or more carried an adjusted odds ratio of 2.39 compared with shorter use.

    Metformin → Risk of biochemical vitamin B12 deficiency during metformin treatment source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/metformin-research/17030830.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f8bbf977dd72887b2d251d3b66ab3ed60bd1917792ebef25f68bf9a8541951f", "start_char": 0, "end_char": 1862, "text_sha256": "0f8bbf977dd72887b2d251d3b66ab3ed60bd1917792ebef25f68bf9a8541951f"}
    experimental_model
    Nested case-control study of 155 cases and 310 matched controls
    exposure
    Current metformin dose and duration
    limitations
    Observational dose-response. Confounding by indication and by diet was adjusted for but cannot be excluded.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Human
    plain_language
    Both a higher dose and a longer time raise the risk, each on its own.
    primary_references
    [metformin-p17030830] Risk factors of vitamin B(12) deficiency in patients receiving metformin. (2006). https://pubmed.ncbi.nlm.nih.gov/17030830/ DOI: 10.1001/archinte.166.18.1975
    tissue_or_cell_type
    Whole body
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1113–1124

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nested case-control study of 155 cases and 310 matched controls · source_derived_draft · unverified_draft

    ### metformin-b12-dose-response Each 1 g/day increment in metformin dose conferred an odds ratio of 2.88 for vitamin B12 deficiency, and use for three years or more carried an adjusted odds ratio of 2.39 compared with shorter use. Condition category: nutrient_deficiency nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Both a higher dose and a longer time raise the risk, each on its own. organism: Human tissue_or_cell_type: Whole body experimental_model: Nested case-control study of 155 cases and 310 matched controls limitations: Observational dose-response. Confounding by indication and by diet was adjusted for but cannot be excluded. exposure: Current metformin dose and duration evidence_span: {"source_cache": "artifacts/metformin-research/17030830.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f8bbf977dd72887b2d251d3b66ab3ed60bd1917792ebef25f68bf9a8541951f", "start_char": 0, "end_char": 1862, "text_sha256": "0f8bbf977dd72887b2d251d3b66ab3ed60bd1917792ebef25f68bf9a8541951f"} [metformin-p17030830] Risk factors of vitamin B(12) deficiency in patients receiving metformin. (2006). https://pubmed.ncbi.nlm.nih.gov/17030830/ DOI: 10.1001/archinte.166.18.1975
    Complete structured claim and evidence

  3. Years of metformin use were associated with increased risk of B12 deficiency, with an odds ratio of 1.13 per year of use, and combined low and borderline-low B12 was more common in the metformin group at both 5 and 13 years.

    Metformin → Risk of biochemical vitamin B12 deficiency during metformin treatment source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/metformin-research/26900641.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09cb74c29fe2d647d668d912a9a01962384e38bcc309a29c429d2caaed3048f1", "start_char": 0, "end_char": 1842, "text_sha256": "09cb74c29fe2d647d668d912a9a01962384e38bcc309a29c429d2caaed3048f1"}
    experimental_model
    Secondary analysis of the Diabetes Prevention Program Outcomes Study over 13 years
    exposure
    Metformin 850 mg twice daily versus placebo, then open-label metformin
    limitations
    Long-duration data. Neuropathy and anaemia were measured as prevalence, and the design cannot separate duration from cumulative dose.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Human
    plain_language
    The risk keeps accumulating the longer the drug is taken.
    primary_references
    [metformin-p26900641] Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. (2016). https://pubmed.ncbi.nlm.nih.gov/26900641/ DOI: 10.1210/jc.2015-3754
    tissue_or_cell_type
    Whole body
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1087–1098

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Secondary analysis of the Diabetes Prevention Program Outcomes Study over 13 years · source_derived_draft · unverified_draft

    ### metformin-b12-duration Years of metformin use were associated with increased risk of B12 deficiency, with an odds ratio of 1.13 per year of use, and combined low and borderline-low B12 was more common in the metformin group at both 5 and 13 years. Condition category: nutrient_deficiency nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The risk keeps accumulating the longer the drug is taken. organism: Human tissue_or_cell_type: Whole body experimental_model: Secondary analysis of the Diabetes Prevention Program Outcomes Study over 13 years limitations: Long-duration data. Neuropathy and anaemia were measured as prevalence, and the design cannot separate duration from cumulative dose. exposure: Metformin 850 mg twice daily versus placebo, then open-label metformin evidence_span: {"source_cache": "artifacts/metformin-research/26900641.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09cb74c29fe2d647d668d912a9a01962384e38bcc309a29c429d2caaed3048f1", "start_char": 0, "end_char": 1842, "text_sha256": "09cb74c29fe2d647d668d912a9a01962384e38bcc309a29c429d2caaed3048f1"} [metformin-p26900641] Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. (2016). https://pubmed.ncbi.nlm.nih.gov/26900641/ DOI: 10.1210/jc.2015-3754
    Complete structured claim and evidence

In the sources

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