{"id":"f56a57fa-a2fd-55b6-aaec-8f2f400d94ea","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-metformin-randomized-status","predicate":"lowered_b12_concentration_in_trial","statement":"Over 4.3 years, metformin lowered B12 concentration by 19% relative to placebo and increased the absolute risk of B12 below 150 pmol/L by 7.2 percentage points (95% CI 2.3–12.1).","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"2f26803a-5d81-53af-8e81-a10aa3c29dee","mechanism_event_label":"Long-term metformin exposure increased biochemical B12 deficiency in this trial.","subject":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"object":{"id":"8390898f-7915-5c30-8ada-c416a386f5f3","slug":"serum-cobalamin-concentration","display_name":"Serum cobalamin concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2f26803a-5d81-53af-8e81-a10aa3c29dee","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-metformin-randomized-status-event","event_type":"observed_intervention","label":"Long-term metformin exposure increased biochemical B12 deficiency in this trial.","description":"Over 4.3 years, metformin lowered B12 concentration by 19% relative to placebo and increased the absolute risk of B12 below 150 pmol/L by 7.2 percentage points (95% CI 2.3–12.1).","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b6d9b937-895d-5e0a-8cc5-0454a0b7d373","slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"},"role":"affected_nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8390898f-7915-5c30-8ada-c416a386f5f3","slug":"serum-cobalamin-concentration","display_name":"Serum cobalamin concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Multicenter randomized placebo-controlled trial: 390 insulin-treated patients with type 2 diabetes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metformin 850 mg three times daily versus placebo for 4.3 years; 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topical membership is not evidence of a direct dietary effect.\nplain_language: Long-term metformin exposure increased biochemical B12 deficiency in this trial.\norganism: Homo sapiens\ntissue_or_cell_type: Human blood or whole-person endpoints\nexperimental_model: Multicenter randomized placebo-controlled trial: 390 insulin-treated patients with type 2 diabetes.\nlimitations: Insulin-treated type 2 diabetes; does not directly establish the absorption mechanism or a neurologic outcome.\nexposure: Metformin 850 mg three times daily versus placebo for 4.3 years; historical experimental exposure.\n[b12-dejager2010] 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","model_system":"Multicenter randomized placebo-controlled trial: 390 insulin-treated patients with type 2 diabetes.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b12-dejager2010] 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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73145023-2982-5848-aff2-8d8875d6b9c5","stable_key":"import-7fc92b9e-9cbf-556e-8719-6b5244625250","title":"Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17)","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":"ad5b3a51d36e856aa7fdfd1cc23f690b094689bad87d28e1a621a54675a01c92","revision_id":"118bd616-0c13-549f-bfeb-bc439715b89c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}