{"id":"44faab35-b6ce-5664-963b-643dc56e2c8d","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-human-hgp-reduction","predicate":"reduces","statement":"Metformin significantly reduced fasting hepatic glucose production from 12.9 to 11.0 micromol/kg/min but did not enhance total body glucose disposal during insulin stimulation.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"7e453a07-087b-5f9b-94db-4e99676d53fd","mechanism_event_label":"In people, the drug works by making the liver release less glucose, not by improving uptake.","subject":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"object":{"id":"827a1499-8877-52c0-b837-0c944dab8fef","slug":"hepatic-glucose-production","display_name":"Hepatic glucose production / endogenous glucose production","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7e453a07-087b-5f9b-94db-4e99676d53fd","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-human-hgp-reduction-event","event_type":"observed_intervention","label":"In people, the drug works by making the liver release less glucose, not by improving uptake.","description":"Metformin significantly reduced fasting hepatic glucose production from 12.9 to 11.0 micromol/kg/min but did not enhance total body glucose disposal during insulin stimulation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9eb0639e-87ee-55fa-b9fd-a242dc8d3189","slug":"glucose-disposal","display_name":"Insulin-mediated whole-body glucose disposal","entity_type_key":"cellular_process"},"role":"unchanged_process","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":"827a1499-8877-52c0-b837-0c944dab8fef","slug":"hepatic-glucose-production","display_name":"Hepatic glucose production / endogenous glucose production","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/metformin-research/8923861.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"164b296465a3d5730d3dba4c66062ce97c227e61b866b6a42c5beb772f51d688\", \"start_char\": 0, \"end_char\": 3516, \"text_sha256\": \"164b296465a3d5730d3dba4c66062ce97c227e61b866b6a42c5beb772f51d688\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Randomised double-blind placebo-controlled trial with tracer infusions and euglycaemic clamp","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"15 weeks of metformin versus placebo in 20 people with type 2 diabetes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Tracer measurement of where the glucose effect comes from. 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Lactate turnover was measured directly and did not change, which bears on lactate safety questions.\nexposure: 15 weeks of metformin versus placebo in 20 people with type 2 diabetes\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/8923861.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"164b296465a3d5730d3dba4c66062ce97c227e61b866b6a42c5beb772f51d688\", \"start_char\": 0, \"end_char\": 3516, \"text_sha256\": \"164b296465a3d5730d3dba4c66062ce97c227e61b866b6a42c5beb772f51d688\"}\n[metformin-p8923861] Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus. (1996). https://pubmed.ncbi.nlm.nih.gov/8923861/ DOI: 10.1210/jcem.81.11.8923861","model_system":"Randomised double-blind placebo-controlled trial with tracer infusions and euglycaemic clamp","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [metformin-p8923861] Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus. (1996). https://pubmed.ncbi.nlm.nih.gov/8923861/ DOI: 10.1210/jcem.81.11.8923861","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. 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