Component

Human OCT1 reduced-function coding variants in the 2007 and 2015 studies

Human OCT1 reduced-function coding variants in the 2007 and 2015 studies. 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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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 it acts on

  1. Carriage of two reduced-function OCT1 alleles was associated with metformin intolerance (odds ratio 2.41), rising to 4.13 in people also taking OCT1-inhibiting drugs.

    Human OCT1 reduced-function coding variants in the 2007 and 2015 studies → Gastrointestinal intolerance of metformin source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/metformin-research/25510240.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8eaf94237679ed7436f863e210d17b13a7219d064e46e7da915ed083c5b04c9", "start_char": 0, "end_char": 1355, "text_sha256": "f8eaf94237679ed7436f863e210d17b13a7219d064e46e7da915ed083c5b04c9"}
    experimental_model
    Case-control comparison of 251 metformin-intolerant and 1915 tolerant people in GoDARTS
    exposure
    Prescribed metformin, OCT1 genotype and co-prescribed OCT1 inhibitors
    limitations
    An association study. Intolerance is self-evidently multifactorial, and the proposed intestinal-concentration mechanism was not measured here.
    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 transporter that controls where the drug goes is also linked to who cannot tolerate it.
    primary_references
    [metformin-p25510240] Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study. (2015). https://pubmed.ncbi.nlm.nih.gov/25510240/ DOI: 10.2337/db14-1388
    tissue_or_cell_type
    Gastrointestinal tolerance

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 359–370

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Case-control comparison of 251 metformin-intolerant and 1915 tolerant people in GoDARTS · source_derived_draft · unverified_draft

    ### metformin-oct1-intolerance Carriage of two reduced-function OCT1 alleles was associated with metformin intolerance (odds ratio 2.41), rising to 4.13 in people also taking OCT1-inhibiting drugs. Condition category: normal 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 transporter that controls where the drug goes is also linked to who cannot tolerate it. organism: Human tissue_or_cell_type: Gastrointestinal tolerance experimental_model: Case-control comparison of 251 metformin-intolerant and 1915 tolerant people in GoDARTS limitations: An association study. Intolerance is self-evidently multifactorial, and the proposed intestinal-concentration mechanism was not measured here. exposure: Prescribed metformin, OCT1 genotype and co-prescribed OCT1 inhibitors evidence_span: {"source_cache": "artifacts/metformin-research/25510240.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8eaf94237679ed7436f863e210d17b13a7219d064e46e7da915ed083c5b04c9", "start_char": 0, "end_char": 1355, "text_sha256": "f8eaf94237679ed7436f863e210d17b13a7219d064e46e7da915ed083c5b04c9"} [metformin-p25510240] Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study. (2015). https://pubmed.ncbi.nlm.nih.gov/25510240/ DOI: 10.2337/db14-1388
    Complete structured claim and evidence

  2. In clinical studies the effects of metformin in glucose tolerance tests were significantly smaller in people carrying reduced-function OCT1 polymorphisms.

    Human OCT1 reduced-function coding variants in the 2007 and 2015 studies → Serum glucose concentration source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"}
    experimental_model
    Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies
    exposure
    Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests
    limitations
    Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Mouse and human, stated per record
    plain_language
    People who carry a weaker version of the transporter responded less to the drug.
    primary_references
    [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558
    tissue_or_cell_type
    Hepatocytes and whole body
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 164–175

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies · source_derived_draft · unverified_draft

    ### metformin-oct1-variants-response In clinical studies the effects of metformin in glucose tolerance tests were significantly smaller in people carrying reduced-function OCT1 polymorphisms. Condition category: machinery_impairment nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: People who carry a weaker version of the transporter responded less to the drug. organism: Mouse and human, stated per record tissue_or_cell_type: Hepatocytes and whole body experimental_model: Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies limitations: Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing. exposure: Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests evidence_span: {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"} [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558
    Complete structured claim and evidence

  3. Seven non-synonymous OCT1 polymorphisms showed reduced metformin uptake, including OCT1-420del, which has normal activity for model substrates.

    Human OCT1 reduced-function coding variants in the 2007 and 2015 studies → Human OCT1-mediated cellular metformin uptake source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"}
    experimental_model
    Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies
    exposure
    Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests
    limitations
    Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Mouse and human, stated per record
    plain_language
    A transporter can look normal on a test substrate and still handle this drug poorly.
    primary_references
    [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558
    tissue_or_cell_type
    Hepatocytes and whole body
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 125–136

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies · source_derived_draft · unverified_draft

    ### metformin-oct1-variants-uptake Seven non-synonymous OCT1 polymorphisms showed reduced metformin uptake, including OCT1-420del, which has normal activity for model substrates. Condition category: machinery_impairment nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: A transporter can look normal on a test substrate and still handle this drug poorly. organism: Mouse and human, stated per record tissue_or_cell_type: Hepatocytes and whole body experimental_model: Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies limitations: Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing. exposure: Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests evidence_span: {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"} [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558
    Complete structured claim and evidence

In the sources

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    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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