{"id":"402d2eb2-c96b-5c9c-ae29-3053a92afabe","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-metformin-dppos-longitudinal","predicate":"longer_exposure_associated_with_more_low_b12_results","statement":"Low B12 (at most 203 pg/mL) was more frequent with metformin at year 5 (4.3% versus 2.3%) but not significantly at year 13 (7.4% versus 5.4%); low-or-borderline B12 (at most 298 pg/mL) remained more frequent at both assessments.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"3ad805cc-b6ee-5277-b851-9a9212d6d535","mechanism_event_label":"The long-term follow-up supports a status association, with different results for different thresholds and visits.","subject":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"object":{"id":"c4a70fb1-aaa6-5136-b609-fbed28fc7331","slug":"low-serum-b12-prevalence","display_name":"Prevalence of low serum B12","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3ad805cc-b6ee-5277-b851-9a9212d6d535","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-metformin-dppos-longitudinal-event","event_type":"observed_intervention","label":"The long-term follow-up supports a status association, with different results for different thresholds and visits.","description":"Low B12 (at most 203 pg/mL) was more frequent with metformin at year 5 (4.3% versus 2.3%) but not significantly at year 13 (7.4% versus 5.4%); low-or-borderline B12 (at most 298 pg/mL) remained more frequent at both assessments.","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":"c4a70fb1-aaa6-5136-b609-fbed28fc7331","slug":"low-serum-b12-prevalence","display_name":"Prevalence of low serum B12","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"DPP/DPPOS secondary analysis: initial randomized metformin/placebo period followed by open-label follow-up. Stored-sample analytic groups: year 5 placebo 857/metformin 858; year 13 placebo 756/metformin 764.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metformin 850 mg twice daily initially; B12 assessed at approximately 5 and 13 years. Long-term exposure is not continuously blinded randomized treatment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Stored-sample subsets and open-label exposure after the initial trial limit continuous randomized interpretation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The long-term follow-up supports a status association, with different results for different thresholds and visits.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b12-aroda2016] 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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human blood or whole-person endpoints","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"25ef55da-5e73-5a06-a9af-00c7a1fe1f4d","evidence_kind":"source_excerpt","locator":"Lines 1649-1659","start_line":1649,"end_line":1659,"excerpt":"### b12-metformin-dppos-longitudinal\nLow B12 (at most 203 pg/mL) was more frequent with metformin at year 5 (4.3% versus 2.3%) but not significantly at year 13 (7.4% versus 5.4%); low-or-borderline B12 (at most 298 pg/mL) remained more frequent at both assessments.\nCondition category: normal\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The long-term follow-up supports a status association, with different results for different thresholds and visits.\norganism: Homo sapiens\ntissue_or_cell_type: Human blood or whole-person endpoints\nexperimental_model: DPP/DPPOS secondary analysis: initial randomized metformin/placebo period followed by open-label follow-up. Stored-sample analytic groups: year 5 placebo 857/metformin 858; year 13 placebo 756/metformin 764.\nlimitations: Stored-sample subsets and open-label exposure after the initial trial limit continuous randomized interpretation.\nexposure: Metformin 850 mg twice daily initially; B12 assessed at approximately 5 and 13 years. Long-term exposure is not continuously blinded randomized treatment.\n[b12-aroda2016] 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","model_system":"DPP/DPPOS secondary analysis: initial randomized metformin/placebo period followed by open-label follow-up. Stored-sample analytic groups: year 5 placebo 857/metformin 858; year 13 placebo 756/metformin 764.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b12-aroda2016] 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","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}