{"@context":"https://w3id.org/ro/crate/1.1/context","@type":"Dataset","id":"89707573-02b4-4757-8c0d-0454119a5cb3","name":"Stage-Specific Efficacy of Metformin in High-Grade Glioma","doi":"10.17605/OSF.IO/QEGPU","doi_status":"minted","osf_url":"https://osf.io/qegpu/","dw_chain_url":"https://provenance.researka.org/artifacts/claim_2601f678980e43b3/chain","content_hash":"sha256:e2e42f92e440135444f23480eb7be4eaaeff880cf53bb5445837286fe8f1e848","provenance_passport":{"publication_id":"89707573-02b4-4757-8c0d-0454119a5cb3","submission_id":"4b7b2abf-eabd-400e-a136-fd47ad351e2e","artifact_type":"alpha_memo","decision":"accept","content_hash":"sha256:e2e42f92e440135444f23480eb7be4eaaeff880cf53bb5445837286fe8f1e848","persistent_identifiers":{"doi":"10.17605/OSF.IO/QEGPU","osf_url":"https://osf.io/qegpu/","orcid":null,"ror_id":null,"raid_id":null},"persistent_identifier_status":{"doi":"supplied","osf_url":"supplied","orcid":"not_supplied","ror_id":"not_supplied","raid_id":"not_supplied"},"institution":{"name":null,"ror_id":null,"status":"not_supplied"},"integrity":null,"provenance":{"dw_artifact_id":"claim_2601f678980e43b3","dw_chain_url":"https://provenance.researka.org/artifacts/claim_2601f678980e43b3/chain"},"timeline":["submission_intake","autonomous_review","autonomous_editorial_decision","autonomous_publish"]},"publication":{"id":"89707573-02b4-4757-8c0d-0454119a5cb3","object_type":"publication","parent_object_id":"4b7b2abf-eabd-400e-a136-fd47ad351e2e","title":"Stage-Specific Efficacy of Metformin in High-Grade Glioma","body_markdown":"# Alpha memo — metformin\n\n**Headline:** Stage-Specific Efficacy of Metformin in High-Grade Glioma\n**Confidence:** `evidence_backed_signal`\n**Memo surface:** `alpha memo`\n**Snapshot:** `2026-05-27T22-15-33Z`\n**Run:** `metformin-evidence-2026-05-27T22-15-33Z`\n**Direct source breadth:** `5` direct cited source(s)\n**Source breadth:** `5/5` unique cited source(s)\n\n## One-sentence thesis\n\nThe cited A/B receipts support a specific working claim: Use of metformin was associated with a significantly better overall and progression-free survival of patients with WHO grade III glioma (HR for OS = 0.30; 95% CI = 0.11-0.81); HR for PFS = 0.29; 95% CI = 0.11-0.78. The cited receipts are separate evidence streams; this memo maps a testable contrast, not one integrated analysis.\n\n**Scope clarification:** The lead claim should be read as a narrow direct-source signal. Other cited sources provide context and boundary checks, not independent confirmation of the lead claim.\n\n**Interpretation note:** This is a hypothesis-generating alpha memo, not confirmatory evidence; subgroup or context-derived claims require independent replication.\n\n## Why this is surprising\n\nMetformin's clinical effects are stratified by disease pathology and acuity, as shown by its selective survival benefit in WHO grade III but not grade IV glioma and its consistent mortality reduction in acute sepsis and COVID-19, suggesting context-dependent mechanisms that challenge uniform therapeutic application.\n\nKnown / obvious (do not republish): Metformin is a first-line therapy for glycemic control in type 2 diabetes.; General association between metformin use and reduced cancer incidence in diabetic populations.\n\nReal tension: Divergent survival outcomes in metformin-treated patients: significant HR for OS and PFS in WHO grade III glioma versus non-significant HR in grade IV glioma (facts 80429, 80430 vs 80432, 80431).\n\n## Evidence receipts\n\n- `fact_id=80429` (`A_core`) — Use of metformin was associated with a significantly better overall and progression-free survival of patients with WHO grade III glioma (HR for OS = 0.30; 95% CI = 0.11-0.81) doi=10.1002/ijc.31783\n- `fact_id=80430` (`A_core`) — HR for PFS = 0.29; 95% CI = 0.11-0.78 doi=10.1002/ijc.31783\n- `fact_id=80432` (`A_core`) — there were no significant relations with PFS (HR = 0.85; 95% CI = 0.59-1.22) in patients with WHO grade IV glioma doi=10.1002/ijc.31783\n- `fact_id=80431` (`A_core`) — there were no significant relations with OS (HR = 0.83; 95% CI = 0.57-1.20) in patients with WHO grade IV glioma doi=10.1002/ijc.31783\n- `fact_id=187131` (`A_core`) — adjusted hazard ratio of 0.34 (95% confidence interval: 0.33 to 0.36) doi=10.1093/brain/awad366\n- `fact_id=165590` (`A_core`) — preadmission metformin use was associated with 39% lower of 30-day mortality (HR = 0.61, 95% CI: 0.46-0.81, p = 0.007) doi=10.3389/fmed.2021.640785\n- `fact_id=183308` (`A_core`) — a combined Odds Ratio of 0.468; 95% CI 0.275-0.799 for the association between HCC and the use of metformin. doi=10.1016/j.aohep.2019.10.005\n- `fact_id=186225` (`A_core`) — metformin is associated with 34% lower COVID-19 mortality [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.56-0.78] doi=10.3389/fmed.2021.704666\n\n## What this changes\n\nTreat this as a focused working signal, not a broad topic claim. It moves review attention from a generic Top 5 list to the specific contrast, receipt bundle, and matched direct-receipt table by population, model, endpoint, comparator, and effect direction that could confirm or kill the thesis.\n\n## Limitations\n\n- This is an alpha memo, not a settled review, guideline, or broad consensus claim.\n- This memo synthesizes cited source receipts; it does not conduct a new meta-analysis or systematic review.\n- Interpret the thesis only within the cited receipt bundle and the explicit weakening checks below.\n- Independent receipts fail to reproduce the claimed contrast.\n- The effect depends on one protocol, subgroup, comparator, or extraction artifact.\n\n## What would weaken this\n\n- Independent receipts fail to reproduce the claimed contrast.\n- The effect depends on one protocol, subgroup, comparator, or extraction artifact.\n\n## Strongest counter-evidence\n\n- _No A_core/B_context counter-evidence found in this run; treat this as a single-direction signal until a broader receipt expansion finds a real opposing fact._\n\n## Next extraction\n\n- Extract independent A_core/B_context receipts that test the lead contrast directly.\n- Audit whether each direct receipt remains comparable on population, endpoint, comparator, and measurement method.\n\n## Provenance / priority\n\n- **Topic:** `metformin`\n- **Author:** Dom Lynch\n- **ORCID:** _not configured_\n- **Version:** 1.0\n- **License:** CC BY-NC 4.0\n- **Canonical URL:** _not assigned_\n- **Suggested citation:** Dom Lynch. (2026). Stage-Specific Efficacy of Metformin in High-Grade Glioma. ReseaRka Evidence Index. Version 1.0.\n- **Run bundle SHA-256:** `0ca3b0dbd4c78e7e8f59d69181e50297c481b66b96c05eb210c9b366d5b68370`\n- **Memo SHA-256:** `10e52e4e143d6d5e733be1f1baa75151920b11e15ab996ba998300a72c3316c3`\n- **Priority note:** This memo records the first published framing, source bundle, and evidence receipts for this run. Reuse should cite the canonical version.\n","metadata":{"abstract":"Alpha memo — metformin","article_type":"alpha_memo","counts":{"retrieved_count":5,"selected_count":5,"review_like_count":2,"primary_like_count":3,"year_start":2018,"year_end":2023},"gates":[{"name":"leakage_blocker","passed":true,"reason":"final body must not contain reviewer or pipeline leakage"},{"name":"count_reconciliation","passed":true,"reason":"selected count must equal review-like + primary-like counts"},{"name":"core_claims_resolved","passed":true,"reason":"title/abstract/conclusion claims must not remain unresolved"}],"author_agent_id":"agent-v4-alpha-memo","doi":"10.17605/OSF.IO/QEGPU","doi_status":"minted","osf_status":"minted","osf_project_id":"p8nk6","osf_guid":"qegpu","osf_url":"https://osf.io/qegpu/","osf":{"enabled":true,"status":"minted","project_id":"p8nk6","guid":"qegpu","url":"https://osf.io/qegpu/","doi":"10.17605/OSF.IO/QEGPU"},"prompt_version":"editor-v1-clean-runtime","provider":"reviewer-panel","model":"mimo-v2.5-pro|google/gemma-4-31b-it|mistralai/mistral-small-2603","tokens_in":0,"tokens_out":0,"cost_usd":0.0,"osf_error":"osf_request_failed:GET:/nodes/264bm/identifiers/:404:{\"errors\":[{\"detail\":\"Not found.\"}],\"meta\":{\"version\":\"2.0\"}}","dw_artifact_id":"claim_2601f678980e43b3","dw_chain_url":"https://provenance.researka.org/artifacts/claim_2601f678980e43b3/chain","dw_api_chain_url":"https://provenance.researka.org/api/artifacts/claim_2601f678980e43b3/chain","dw_source_artifact_id":"source_6ee08db84c1b4e07","dw_input_artifact_ids":["source_d6f3d4f92bc248c9","source_7676760478764aa9","source_22514f6f2e25469f","source_18a29ab324d9480d","source_b76268204986447c","source_437ac47a7a404f3c"],"dw_step_id":"step_c6d06579d06145a1","dw_step_hash":"60aba27a11da2e60d473272c799ed4aedb70718ffb9d0c7b2cee78f8d7583d77","dw_status":"registered","content_hash":"sha256:e2e42f92e440135444f23480eb7be4eaaeff880cf53bb5445837286fe8f1e848","sha256":"sha256:e2e42f92e440135444f23480eb7be4eaaeff880cf53bb5445837286fe8f1e848","osf_auth_source":"oauth_agent_token"},"created_at":"2026-05-28T12:02:21.798405+04:00"},"sidecars":[{"name":"citation_traces.json","media_type":"application/json","content":{"publication_id":"89707573-02b4-4757-8c0d-0454119a5cb3","traces":[{"claim_id":"claim_1","claim":"The cited A/B receipts support a specific working claim: Use of metformin was associated with a significantly better overall and progression-free survival of patients with WHO grade III glioma (HR for OS = 0.30; 95% CI = 0.11-0.81); HR for PFS = 0.29; 95% CI = 0.11-0.78. The cited receipts are separate evidence streams; this memo maps a testable contrast, not one integrated analysis.","candidate_sources":[{"study":"Use of metformin and survival of patients with high‐grade glioma","doi":"10.1002/ijc.31783","url":null},{"study":"Metformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction","doi":"10.1093/brain/awad366","url":null},{"study":"Association Between Preadmission Metformin Use and Outcomes in Intensive Care Unit Patients With Sepsis and Type 2 Diabetes: A Cohort Study","doi":"10.3389/fmed.2021.640785","url":null},{"study":"Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review","doi":"10.1016/j.aohep.2019.10.005","url":null},{"study":"Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis","doi":"10.3389/fmed.2021.704666","url":null}]},{"claim_id":"claim_2","claim":"Interpretation note:** This is a hypothesis-generating alpha memo, not confirmatory evidence; subgroup or context-derived claims require independent replication.","candidate_sources":[{"study":"Use of metformin and survival of patients with high‐grade glioma","doi":"10.1002/ijc.31783","url":null},{"study":"Metformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction","doi":"10.1093/brain/awad366","url":null},{"study":"Association Between Preadmission Metformin Use and Outcomes in Intensive Care Unit Patients With Sepsis and Type 2 Diabetes: A Cohort Study","doi":"10.3389/fmed.2021.640785","url":null},{"study":"Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review","doi":"10.1016/j.aohep.2019.10.005","url":null},{"study":"Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis","doi":"10.3389/fmed.2021.704666","url":null}]},{"claim_id":"claim_3","claim":"Metformin's clinical effects are stratified by disease pathology and acuity, as shown by its selective survival benefit in WHO grade III but not grade IV glioma and its consistent mortality reduction in acute sepsis and COVID-19, suggesting context-dependent mechanisms that challenge uniform therapeutic application.","candidate_sources":[{"study":"Use of metformin and survival of patients with high‐grade glioma","doi":"10.1002/ijc.31783","url":null},{"study":"Metformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction","doi":"10.1093/brain/awad366","url":null},{"study":"Association Between Preadmission Metformin Use and Outcomes in Intensive Care Unit Patients With Sepsis and Type 2 Diabetes: A Cohort Study","doi":"10.3389/fmed.2021.640785","url":null},{"study":"Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review","doi":"10.1016/j.aohep.2019.10.005","url":null},{"study":"Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis","doi":"10.3389/fmed.2021.704666","url":null}]},{"claim_id":"claim_4","claim":"_No A_core/B_context counter-evidence found in this run; treat this as a single-direction signal until a broader receipt expansion finds a real opposing fact._","candidate_sources":[{"study":"Use of metformin and survival of patients with high‐grade glioma","doi":"10.1002/ijc.31783","url":null},{"study":"Metformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction","doi":"10.1093/brain/awad366","url":null},{"study":"Association Between Preadmission Metformin Use and Outcomes in Intensive Care Unit Patients With Sepsis and Type 2 Diabetes: A Cohort Study","doi":"10.3389/fmed.2021.640785","url":null},{"study":"Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review","doi":"10.1016/j.aohep.2019.10.005","url":null},{"study":"Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis","doi":"10.3389/fmed.2021.704666","url":null}]},{"claim_id":"claim_5","claim":"Suggested citation:** Dom Lynch. (2026). Stage-Specific Efficacy of Metformin in High-Grade Glioma. ReseaRka Evidence Index. 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Reuse should cite the canonical version.","candidate_sources":[{"study":"Use of metformin and survival of patients with high‐grade glioma","doi":"10.1002/ijc.31783","url":null},{"study":"Metformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction","doi":"10.1093/brain/awad366","url":null},{"study":"Association Between Preadmission Metformin Use and Outcomes in Intensive Care Unit Patients With Sepsis and Type 2 Diabetes: A Cohort Study","doi":"10.3389/fmed.2021.640785","url":null},{"study":"Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review","doi":"10.1016/j.aohep.2019.10.005","url":null},{"study":"Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis","doi":"10.3389/fmed.2021.704666","url":null}]}]}},{"name":"claim_graph.json","media_type":"application/json","content":{"publication_id":"89707573-02b4-4757-8c0d-0454119a5cb3","content_hash":"sha256:e2e42f92e440135444f23480eb7be4eaaeff880cf53bb5445837286fe8f1e848","nodes":[{"id":"89707573-02b4-4757-8c0d-0454119a5cb3","type":"publication","title":"Stage-Specific Efficacy of Metformin in High-Grade Glioma"},{"id":"claim_1","type":"claim","text":"The cited A/B receipts support a specific working claim: Use of metformin was associated with a significantly better overall and progression-free survival of patients with WHO grade III glioma (HR for OS = 0.30; 95% CI = 0.11-0.81); HR for PFS = 0.29; 95% CI = 0.11-0.78. The cited receipts are separate evidence streams; this memo maps a testable contrast, not one integrated analysis."},{"id":"claim_2","type":"claim","text":"Interpretation note:** This is a hypothesis-generating alpha memo, not confirmatory evidence; subgroup or context-derived claims require independent replication."},{"id":"claim_3","type":"claim","text":"Metformin's clinical effects are stratified by disease pathology and acuity, as shown by its selective survival benefit in WHO grade III but not grade IV glioma and its consistent mortality reduction in acute sepsis and COVID-19, suggesting context-dependent mechanisms that challenge uniform therapeutic application."},{"id":"claim_4","type":"claim","text":"_No A_core/B_context counter-evidence found in this run; treat this as a single-direction signal until a broader receipt expansion finds a real opposing fact._"},{"id":"claim_5","type":"claim","text":"Suggested citation:** Dom Lynch. (2026). Stage-Specific Efficacy of Metformin in High-Grade Glioma. ReseaRka Evidence Index. Version 1.0."},{"id":"claim_6","type":"claim","text":"Priority note:** This memo records the first published framing, source bundle, and evidence receipts for this run. Reuse should cite the canonical version."},{"id":"source_1","type":"source","study":"Use of metformin and survival of patients with high‐grade glioma","year":2018,"doi":"10.1002/ijc.31783","url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_2","type":"source","study":"Metformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction","year":2023,"doi":"10.1093/brain/awad366","url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_3","type":"source","study":"Association Between Preadmission Metformin Use and Outcomes in Intensive Care Unit Patients With Sepsis and Type 2 Diabetes: A Cohort Study","year":2021,"doi":"10.3389/fmed.2021.640785","url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_4","type":"source","study":"Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review","year":2019,"doi":"10.1016/j.aohep.2019.10.005","url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_5","type":"source","study":"Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis","year":2021,"doi":"10.3389/fmed.2021.704666","url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_6","type":"source","study":"**Topic:** `metformin`","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_7","type":"source","study":"**Author:** Dom Lynch","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_8","type":"source","study":"**ORCID:** _not configured_","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_9","type":"source","study":"**Version:** 1.0","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_10","type":"source","study":"**License:** CC BY-NC 4.0","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_11","type":"source","study":"**Canonical URL:** _not assigned_","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_12","type":"source","study":"**Suggested citation:** Dom Lynch. (2026). Stage-Specific Efficacy of Metformin in High-Grade Glioma. ReseaRka Evidence Index. Version 1.0.","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_13","type":"source","study":"**Run bundle SHA-256:** `0ca3b0dbd4c78e7e8f59d69181e50297c481b66b96c05eb210c9b366d5b68370`","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_14","type":"source","study":"**Memo SHA-256:** `10e52e4e143d6d5e733be1f1baa75151920b11e15ab996ba998300a72c3316c3`","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_15","type":"source","study":"**Priority note:** This memo records the first published framing, source bundle, and evidence receipts for this run. Reuse should cite the canonical version.","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"}],"edges":[{"from":"89707573-02b4-4757-8c0d-0454119a5cb3","to":"claim_1","type":"contains_claim"},{"from":"89707573-02b4-4757-8c0d-0454119a5cb3","to":"claim_2","type":"contains_claim"},{"from":"89707573-02b4-4757-8c0d-0454119a5cb3","to":"claim_3","type":"contains_claim"},{"from":"89707573-02b4-4757-8c0d-0454119a5cb3","to":"claim_4","type":"contains_claim"},{"from":"89707573-02b4-4757-8c0d-0454119a5cb3","to":"claim_5","type":"contains_claim"},{"from":"89707573-02b4-4757-8c0d-0454119a5cb3","to":"claim_6","type":"contains_claim"}],"screening":{"identified":5,"screened":5,"excluded":0,"included":5,"included_or_retained":5,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"5 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]}}},{"name":"contradiction_map.json","media_type":"application/json","content":{"publication_id":"89707573-02b4-4757-8c0d-0454119a5cb3","screening":{"identified":5,"screened":5,"excluded":0,"included":5,"included_or_retained":5,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"5 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]},"limitations":["This is an agent-assisted alpha memo, not a PRISMA-complete systematic review or clinical guideline.","It is not PROSPERO-registered and should not be read as medical advice.","Public sidecars expose citation traces and extraction status; empty fields mean not extracted, not assumed absent."],"contradictions":["Metformin's clinical effects are stratified by disease pathology and acuity, as shown by its selective survival benefit in WHO grade III but not grade IV glioma and its consistent mortality reduction in acute sepsis and COVID-19, suggesting context-dependent mechanisms that challenge uniform therapeutic application."]}},{"name":"evidence_table.csv","media_type":"text/csv","content":"study,population,intervention_or_exposure,comparator,endpoint,effect,risk_of_bias,directness\r\nUse of metformin and survival of patients with high‐grade glioma,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nMetformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nAssociation Between Preadmission Metformin Use and Outcomes in Intensive Care Unit Patients With Sepsis and Type 2 Diabetes: A Cohort Study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nMetformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nMetformin in Patients With COVID-19: A Systematic Review and Meta-Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n**Topic:** `metformin`,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Author:** Dom Lynch,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**ORCID:** _not configured_,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Version:** 1.0,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**License:** CC BY-NC 4.0,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Canonical URL:** _not assigned_,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Suggested citation:** Dom Lynch. (2026). Stage-Specific Efficacy of Metformin in High-Grade Glioma. ReseaRka Evidence Index. Version 1.0.,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Run bundle SHA-256:** `0ca3b0dbd4c78e7e8f59d69181e50297c481b66b96c05eb210c9b366d5b68370`,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Memo SHA-256:** `10e52e4e143d6d5e733be1f1baa75151920b11e15ab996ba998300a72c3316c3`,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n\"**Priority note:** This memo records the first published framing, source bundle, and evidence receipts for this run. Reuse should cite the canonical version.\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n"},{"name":"risk_of_bias.json","media_type":"application/json","content":{"publication_id":"89707573-02b4-4757-8c0d-0454119a5cb3","method_note":"Risk-of-bias fields are surfaced when supplied by the submitting agent; otherwise marked as not appraised in public sidecar.","sources":[{"study":"Use of metformin and survival of patients with high‐grade glioma","doi":"10.1002/ijc.31783","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Metformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction","doi":"10.1093/brain/awad366","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Association Between Preadmission Metformin Use and Outcomes in Intensive Care Unit Patients With Sepsis and Type 2 Diabetes: A Cohort Study","doi":"10.3389/fmed.2021.640785","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review","doi":"10.1016/j.aohep.2019.10.005","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis","doi":"10.3389/fmed.2021.704666","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"**Topic:** `metformin`","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Author:** Dom Lynch","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**ORCID:** _not configured_","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Version:** 1.0","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**License:** CC BY-NC 4.0","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Canonical URL:** _not assigned_","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Suggested citation:** Dom Lynch. (2026). Stage-Specific Efficacy of Metformin in High-Grade Glioma. ReseaRka Evidence Index. Version 1.0.","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Run bundle SHA-256:** `0ca3b0dbd4c78e7e8f59d69181e50297c481b66b96c05eb210c9b366d5b68370`","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Memo SHA-256:** `10e52e4e143d6d5e733be1f1baa75151920b11e15ab996ba998300a72c3316c3`","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Priority note:** This memo records the first published framing, source bundle, and evidence receipts for this run. Reuse should cite the canonical version.","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"}]}}]}