{"id":"e0ec1045-8cc6-516f-81d3-63e9cd8129ef","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-b12-dose-response","predicate":"increases","statement":"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.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"d88db6d1-cd41-572c-b8c1-3ad39593e32e","mechanism_event_label":"Both a higher dose and a longer time raise the risk, each on its own.","subject":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"object":{"id":"365edc29-29f1-5cfa-9a48-78db46d845ae","slug":"metformin-b12-deficiency-risk","display_name":"Risk of biochemical vitamin B12 deficiency during metformin treatment","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d88db6d1-cd41-572c-b8c1-3ad39593e32e","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-b12-dose-response-event","event_type":"observed_intervention","label":"Both a higher dose and a longer time raise the risk, each on its own.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"365edc29-29f1-5cfa-9a48-78db46d845ae","slug":"metformin-b12-deficiency-risk","display_name":"Risk of biochemical vitamin B12 deficiency during metformin treatment","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"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\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Nested case-control study of 155 cases and 310 matched controls","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Current metformin dose and duration","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Observational dose-response. 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(2006). https://pubmed.ncbi.nlm.nih.gov/17030830/ DOI: 10.1001/archinte.166.18.1975","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Whole body","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"cd484fd8-a1f2-5f80-9368-1cd831a1bb1f","evidence_kind":"source_excerpt","locator":"Lines 1113-1124","start_line":1113,"end_line":1124,"excerpt":"### metformin-b12-dose-response\nEach 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.\nCondition category: nutrient_deficiency\nnutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.\nplain_language: Both a higher dose and a longer time raise the risk, each on its own.\norganism: Human\ntissue_or_cell_type: Whole body\nexperimental_model: Nested case-control study of 155 cases and 310 matched controls\nlimitations: Observational dose-response. Confounding by indication and by diet was adjusted for but cannot be excluded.\nexposure: Current metformin dose and duration\nevidence_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\"}\n[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","model_system":"Nested case-control study of 155 cases and 310 matched controls","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study 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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d0474bd9-7cfd-5695-a152-12f3633a6813","stable_key":"import-8b3cf083-ea9c-54f5-b42b-bf1fef5b2978","title":"Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"0b51d0759aeeb88ac5b3a6277245a196b2bb024d7c32ec89379ed428fb06bfb5","revision_id":"0405c75e-f06e-5af7-a642-1777802f6004","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}