Serum glucose concentration

What acts on it

1. The 15-person uncontrolled pilot reported lower fasting glucose after procynZ-45 exposure.

   C. zeylanicum procynZ-45 polyphenol extract → Serum glucose concentration source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/ceylon-research/25051315.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a6dc6fe3a75793687a15c6ce73ab8ae07dbf8541c5b329d2f35c1a42922d5bb", "start_char": 0, "end_char": 1406, "text_sha256": "3a6dc6fe3a75793687a15c6ce73ab8ae07dbf8541c5b329d2f35c1a42922d5bb"}

   experimental_model

   Extract comparison in diabetic rats plus uncontrolled human pilot

   exposure

   Rats 200 mg/kg for 30 days; 15 unmedicated adults, procynZ-45 125 mg twice daily for 30 days

   limitations

   GAE denotes assay standardization, not proof that 45% of extract mass is a single polyphenol. Human pilot lacked a randomized control.

   nutrient_topic

   Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

   organism

   Human

   plain_language

   Glucose fell during a small pilot, but without a control group the extract’s causal effect is uncertain.

   primary_references

   [ceylon-p25051315] Effects of the polyphenol content on the anti-diabetic activity of Cinnamomum zeylanicum extracts. (2014). https://pubmed.ncbi.nlm.nih.gov/25051315/ DOI: 10.1039/c4fo00130c

   tissue_or_cell_type

   Metabolic measurements

   Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 1091–1102

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Extract comparison in diabetic rats plus uncontrolled human pilot · source_derived_draft · unverified_draft

   ### ceylon-procynz-glucose The 15-person uncontrolled pilot reported lower fasting glucose after procynZ-45 exposure. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glucose fell during a small pilot, but without a control group the extract’s causal effect is uncertain. organism: Human tissue_or_cell_type: Metabolic measurements experimental_model: Extract comparison in diabetic rats plus uncontrolled human pilot limitations: GAE denotes assay standardization, not proof that 45% of extract mass is a single polyphenol. Human pilot lacked a randomized control. exposure: Rats 200 mg/kg for 30 days; 15 unmedicated adults, procynZ-45 125 mg twice daily for 30 days evidence_span: {"source_cache": "artifacts/ceylon-research/25051315.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a6dc6fe3a75793687a15c6ce73ab8ae07dbf8541c5b329d2f35c1a42922d5bb", "start_char": 0, "end_char": 1406, "text_sha256": "3a6dc6fe3a75793687a15c6ce73ab8ae07dbf8541c5b329d2f35c1a42922d5bb"} [ceylon-p25051315] Effects of the polyphenol content on the anti-diabetic activity of Cinnamomum zeylanicum extracts. (2014). https://pubmed.ncbi.nlm.nih.gov/25051315/ DOI: 10.1039/c4fo00130c

   Complete structured claim and evidence

2. Fasting glucose reduction favored extract by an adjusted 8.59 mg/dL, 95% CI 0.59–16.59, p=0.036, on the secondary endpoint.

   C. zeylanicum standardized extract in the 2025 LDL trial → Serum glucose concentration source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/ceylon-research/39854533.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5a891f5ed9907674aa119b8c697d009c06017b11d7e21e7959013853e3fd3443", "start_char": 0, "end_char": 2414, "text_sha256": "5a891f5ed9907674aa119b8c697d009c06017b11d7e21e7959013853e3fd3443"}

   experimental_model

   Double-blind placebo-controlled randomized trial, complete-case analysis

   exposure

   150 randomized, 127 assessed at 12 weeks; standardized extract 1000 mg/day

   limitations

   LDL was primary and nonsignificant; fasting glucose was secondary. Missing follow-up, baseline metabolic status and preparation constrain generalization.

   nutrient_topic

   Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

   organism

   Human

   plain_language

   The trial found a modest fasting-glucose signal, even though its main cholesterol result was negative.

   primary_references

   [ceylon-p39854533] Effects of Cinnamomum zeylanicum (Ceylon cinnamon) extract on lipid profile, glucose levels and its safety in adults: A randomized, double-blind, controlled trial. (2025). https://pubmed.ncbi.nlm.nih.gov/39854533/ DOI: 10.1371/journal.pone.0317904

   tissue_or_cell_type

   Adults with LDL-C 100–190 mg/dL

   Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 1156–1167

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled randomized trial, complete-case analysis · source_derived_draft · unverified_draft

   ### ceylon-trial-glucose Fasting glucose reduction favored extract by an adjusted 8.59 mg/dL, 95% CI 0.59–16.59, p=0.036, on the secondary endpoint. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial found a modest fasting-glucose signal, even though its main cholesterol result was negative. organism: Human tissue_or_cell_type: Adults with LDL-C 100–190 mg/dL experimental_model: Double-blind placebo-controlled randomized trial, complete-case analysis limitations: LDL was primary and nonsignificant; fasting glucose was secondary. Missing follow-up, baseline metabolic status and preparation constrain generalization. exposure: 150 randomized, 127 assessed at 12 weeks; standardized extract 1000 mg/day evidence_span: {"source_cache": "artifacts/ceylon-research/39854533.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5a891f5ed9907674aa119b8c697d009c06017b11d7e21e7959013853e3fd3443", "start_char": 0, "end_char": 2414, "text_sha256": "5a891f5ed9907674aa119b8c697d009c06017b11d7e21e7959013853e3fd3443"} [ceylon-p39854533] Effects of Cinnamomum zeylanicum (Ceylon cinnamon) extract on lipid profile, glucose levels and its safety in adults: A randomized, double-blind, controlled trial. (2025). https://pubmed.ncbi.nlm.nih.gov/39854533/ DOI: 10.1371/journal.pone.0317904

   Complete structured claim and evidence

3. Serum glucose did not differ significantly between groups.

   Mangiferin → Serum glucose concentration source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/mangiferin-research/25989216.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f57445ffe1eb20de3c2bf1170d152c358be1d7763cef2a091c0b3052040e539", "start_char": 0, "end_char": 1522, "text_sha256": "2f57445ffe1eb20de3c2bf1170d152c358be1d7763cef2a091c0b3052040e539"}

   experimental_model

   Double-blind randomized placebo-controlled trial

   exposure

   Mangiferin 150 mg/day for 12 weeks

   limitations

   One trial in a selected population; biomarkers do not demonstrate clinical outcomes or directly measure fatty-acid flux.

   nutrient_topic

   Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin

   organism

   Overweight adults with hyperlipidemia; 97 completers

   plain_language

   The trial did not demonstrate improvement in every glucose endpoint.

   primary_references

   [mangiferin-p25989216] Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/25989216/ DOI: 10.1038/srep10344

   tissue_or_cell_type

   Serum metabolic measurements

   Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 1251–1262

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled trial · source_derived_draft · unverified_draft

   ### mangiferin-trial-glucose-null Serum glucose did not differ significantly between groups. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial did not demonstrate improvement in every glucose endpoint. organism: Overweight adults with hyperlipidemia; 97 completers tissue_or_cell_type: Serum metabolic measurements experimental_model: Double-blind randomized placebo-controlled trial limitations: One trial in a selected population; biomarkers do not demonstrate clinical outcomes or directly measure fatty-acid flux. exposure: Mangiferin 150 mg/day for 12 weeks evidence_span: {"source_cache": "artifacts/mangiferin-research/25989216.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f57445ffe1eb20de3c2bf1170d152c358be1d7763cef2a091c0b3052040e539", "start_char": 0, "end_char": 1522, "text_sha256": "2f57445ffe1eb20de3c2bf1170d152c358be1d7763cef2a091c0b3052040e539"} [mangiferin-p25989216] Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/25989216/ DOI: 10.1038/srep10344

   Complete structured claim and evidence

4. The zinc-magnesium-chromium regimen did not significantly improve measured metabolic-syndrome risk components, including serum glucose, relative to placebo.

   Chromium → Serum glucose concentration source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/chromium-research/29773176.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6107419f3b2f125a5a9971f56f24c1bd454a97512ef432f154c79d26b85c1067", "start_char": 0, "end_char": 1208, "text_sha256": "6107419f3b2f125a5a9971f56f24c1bd454a97512ef432f154c79d26b85c1067"}

   experimental_model

   Double-blind randomized placebo-controlled trial; 32 adults

   exposure

   24 weeks: 300 mg magnesium, 600 µg chromium and 36 mg zinc daily versus placebo

   limitations

   Only the three-mineral combination was tested; individual effects and synergy cannot be separated. Small sample and multiple endpoints.

   nutrient_topic

   Chromium research collection; topical membership is not evidence of a direct dietary effect. · Chromium

   organism

   Human with metabolic syndrome

   plain_language

   Adding three minerals did not consistently improve the metabolic endpoints in this small trial.

   primary_references

   [chromium-p29773176] Effects of zinc, magnesium, and chromium supplementation on cardiometabolic risk in adults with metabolic syndrome: A double-blind, placebo-controlled randomised trial. (2018). https://pubmed.ncbi.nlm.nih.gov/29773176/ DOI: 10.1016/j.jtemb.2018.03.022

   tissue_or_cell_type

   Circulating glucose; the paper describes serum glucose rather than a tissue-specific transport endpoint

   Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 627–638

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled trial; 32 adults · source_derived_draft · unverified_draft

   ### chromium-triple-mineral-glycemia-null The zinc-magnesium-chromium regimen did not significantly improve measured metabolic-syndrome risk components, including serum glucose, relative to placebo. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding three minerals did not consistently improve the metabolic endpoints in this small trial. organism: Human with metabolic syndrome tissue_or_cell_type: Circulating glucose; the paper describes serum glucose rather than a tissue-specific transport endpoint experimental_model: Double-blind randomized placebo-controlled trial; 32 adults limitations: Only the three-mineral combination was tested; individual effects and synergy cannot be separated. Small sample and multiple endpoints. exposure: 24 weeks: 300 mg magnesium, 600 µg chromium and 36 mg zinc daily versus placebo evidence_span: {"source_cache": "artifacts/chromium-research/29773176.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6107419f3b2f125a5a9971f56f24c1bd454a97512ef432f154c79d26b85c1067", "start_char": 0, "end_char": 1208, "text_sha256": "6107419f3b2f125a5a9971f56f24c1bd454a97512ef432f154c79d26b85c1067"} [chromium-p29773176] Effects of zinc, magnesium, and chromium supplementation on cardiometabolic risk in adults with metabolic syndrome: A double-blind, placebo-controlled randomised trial. (2018). https://pubmed.ncbi.nlm.nih.gov/29773176/ DOI: 10.1016/j.jtemb.2018.03.022

   Complete structured claim and evidence

5. Metformin retained its ability to lower circulating glucose in the absence of GDF15 activity.

   Metformin → Serum glucose concentration source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/metformin-research/31875646.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a25b31ade3977aabe24159b0374c42fe4fb48ab1464ba9ae69c73e63f41e742a", "start_char": 0, "end_char": 1454, "text_sha256": "a25b31ade3977aabe24159b0374c42fe4fb48ab1464ba9ae69c73e63f41e742a"}

   experimental_model

   Two randomised controlled trials in people plus wild-type, Gdf15-null and Gfral-null mice

   exposure

   Oral metformin; high-fat diet in mice; GFRAL-antagonist antibody

   limitations

   The weight mechanism is separable from the glucose mechanism in this work; the mouse knockouts carry the causal claim, the human trials the GDF15 rise. A publisher correction was issued for this paper (Nature 2020;578:E24, PMID 32051582); its notice body was not available, so its impact on these records has not been assessed.

   nutrient_topic

   Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

   organism

   Human and mouse

   plain_language

   Weight and glucose are two different effects with different routes.

   primary_references

   [metformin-p31875646] GDF15 mediates the effects of metformin on body weight and energy balance. (2020). https://pubmed.ncbi.nlm.nih.gov/31875646/ DOI: 10.1038/s41586-019-1911-y

   tissue_or_cell_type

   Distal intestine, kidney and brainstem receptor

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 801–812

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two randomised controlled trials in people plus wild-type, Gdf15-null and Gfral-null mice · source_derived_draft · unverified_draft

   ### metformin-gdf15-glucose-separable Metformin retained its ability to lower circulating glucose in the absence of GDF15 activity. Condition category: machinery_impairment nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Weight and glucose are two different effects with different routes. organism: Human and mouse tissue_or_cell_type: Distal intestine, kidney and brainstem receptor experimental_model: Two randomised controlled trials in people plus wild-type, Gdf15-null and Gfral-null mice limitations: The weight mechanism is separable from the glucose mechanism in this work; the mouse knockouts carry the causal claim, the human trials the GDF15 rise. A publisher correction was issued for this paper (Nature 2020;578:E24, PMID 32051582); its notice body was not available, so its impact on these records has not been assessed. exposure: Oral metformin; high-fat diet in mice; GFRAL-antagonist antibody evidence_span: {"source_cache": "artifacts/metformin-research/31875646.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a25b31ade3977aabe24159b0374c42fe4fb48ab1464ba9ae69c73e63f41e742a", "start_char": 0, "end_char": 1454, "text_sha256": "a25b31ade3977aabe24159b0374c42fe4fb48ab1464ba9ae69c73e63f41e742a"} [metformin-p31875646] GDF15 mediates the effects of metformin on body weight and energy balance. (2020). https://pubmed.ncbi.nlm.nih.gov/31875646/ DOI: 10.1038/s41586-019-1911-y

   Complete structured claim and evidence

6. Delayed-release metformin targeted to the ileum produced similar reductions in fasting and postprandial glucose despite an almost 60% reduction in systemic metformin exposure compared with immediate-release metformin.

   Metformin → Serum glucose concentration source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/metformin-research/27216492.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c874a5c13e2e709b4b36040f281e2b187e7956b4610decddc35403170c0ed45d", "start_char": 0, "end_char": 3863, "text_sha256": "c874a5c13e2e709b4b36040f281e2b187e7956b4610decddc35403170c0ed45d"}

   experimental_model

   Two randomised crossover trials of delayed-release metformin targeted to the ileum

   exposure

   Delayed-release versus immediate-release metformin over 5 to 7 day periods

   limitations

   The dissociation of effect from plasma exposure is the key observation. Funded by the manufacturer of the delayed-release formulation, which the record retains.

   nutrient_topic

   Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

   organism

   Human

   plain_language

   The drug can work from inside the gut without much of it entering the blood.

   primary_references

   [metformin-p27216492] Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. (2016). https://pubmed.ncbi.nlm.nih.gov/27216492/ DOI: 10.1007/s00125-016-3992-6

   tissue_or_cell_type

   Distal small intestine

   Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 827–838

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two randomised crossover trials of delayed-release metformin targeted to the ileum · source_derived_draft · unverified_draft

   ### metformin-gut-restricted-effect Delayed-release metformin targeted to the ileum produced similar reductions in fasting and postprandial glucose despite an almost 60% reduction in systemic metformin exposure compared with immediate-release metformin. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The drug can work from inside the gut without much of it entering the blood. organism: Human tissue_or_cell_type: Distal small intestine experimental_model: Two randomised crossover trials of delayed-release metformin targeted to the ileum limitations: The dissociation of effect from plasma exposure is the key observation. Funded by the manufacturer of the delayed-release formulation, which the record retains. exposure: Delayed-release versus immediate-release metformin over 5 to 7 day periods evidence_span: {"source_cache": "artifacts/metformin-research/27216492.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c874a5c13e2e709b4b36040f281e2b187e7956b4610decddc35403170c0ed45d", "start_char": 0, "end_char": 3863, "text_sha256": "c874a5c13e2e709b4b36040f281e2b187e7956b4610decddc35403170c0ed45d"} [metformin-p27216492] Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials. (2016). https://pubmed.ncbi.nlm.nih.gov/27216492/ DOI: 10.1007/s00125-016-3992-6

   Complete structured claim and evidence

7. Metformin required LKB1 in the liver to lower blood glucose levels in these mice.

   Liver-specific LKB1-deficient mouse hepatocytes in the 2010 and 2005 studies → Serum glucose concentration source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/metformin-research/16308421.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4762199db357f0f8002a9da8ff2ecad8e9bfcb48c963eb4b2cde7ffa363eec4", "start_char": 0, "end_char": 1103, "text_sha256": "e4762199db357f0f8002a9da8ff2ecad8e9bfcb48c963eb4b2cde7ffa363eec4"}

   experimental_model

   Liver-specific LKB1 deletion in adult mice with adenoviral TORC2 knockdown

   exposure

   Metformin in LKB1-deficient livers

   limitations

   A genetic requirement in this model. The same year’s consensus was later challenged by AMPK-independent findings recorded in this collection.

   nutrient_topic

   Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

   organism

   Mouse

   plain_language

   Without the upstream kinase, the drug did not lower glucose in this model.

   primary_references

   [metformin-p16308421] The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. (2005). https://pubmed.ncbi.nlm.nih.gov/16308421/ DOI: 10.1126/science.1120781

   tissue_or_cell_type

   Liver

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 580–591

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Liver-specific LKB1 deletion in adult mice with adenoviral TORC2 knockdown · source_derived_draft · unverified_draft

   ### metformin-lkb1-required-metformin Metformin required LKB1 in the liver to lower blood glucose levels in these mice. Condition category: machinery_impairment nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Without the upstream kinase, the drug did not lower glucose in this model. organism: Mouse tissue_or_cell_type: Liver experimental_model: Liver-specific LKB1 deletion in adult mice with adenoviral TORC2 knockdown limitations: A genetic requirement in this model. The same year’s consensus was later challenged by AMPK-independent findings recorded in this collection. exposure: Metformin in LKB1-deficient livers evidence_span: {"source_cache": "artifacts/metformin-research/16308421.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4762199db357f0f8002a9da8ff2ecad8e9bfcb48c963eb4b2cde7ffa363eec4", "start_char": 0, "end_char": 1103, "text_sha256": "e4762199db357f0f8002a9da8ff2ecad8e9bfcb48c963eb4b2cde7ffa363eec4"} [metformin-p16308421] The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. (2005). https://pubmed.ncbi.nlm.nih.gov/16308421/ DOI: 10.1126/science.1120781

   Complete structured claim and evidence

8. In Oct1-deficient mice the glucose-lowering effects of metformin were completely abolished.

   Experimental Oct1-null mouse genotype → Serum glucose concentration source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"}

   experimental_model

   Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies

   exposure

   Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests

   limitations

   Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing.

   nutrient_topic

   Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

   organism

   Mouse and human, stated per record

   plain_language

   The whole glucose effect depended on the drug reaching the liver in this model.

   primary_references

   [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558

   tissue_or_cell_type

   Hepatocytes and whole body

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 151–162

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies · source_derived_draft · unverified_draft

   ### metformin-oct1-null-glucose In Oct1-deficient mice the glucose-lowering effects of metformin were completely abolished. Condition category: machinery_impairment nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The whole glucose effect depended on the drug reaching the liver in this model. organism: Mouse and human, stated per record tissue_or_cell_type: Hepatocytes and whole body experimental_model: Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies limitations: Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing. exposure: Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests evidence_span: {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"} [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558

   Complete structured claim and evidence

9. In clinical studies the effects of metformin in glucose tolerance tests were significantly smaller in people carrying reduced-function OCT1 polymorphisms.

   Human OCT1 reduced-function coding variants in the 2007 and 2015 studies → Serum glucose concentration source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"}

   experimental_model

   Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies

   exposure

   Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests

   limitations

   Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing.

   nutrient_topic

   Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

   organism

   Mouse and human, stated per record

   plain_language

   People who carry a weaker version of the transporter responded less to the drug.

   primary_references

   [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558

   tissue_or_cell_type

   Hepatocytes and whole body

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 164–175

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies · source_derived_draft · unverified_draft

   ### metformin-oct1-variants-response In clinical studies the effects of metformin in glucose tolerance tests were significantly smaller in people carrying reduced-function OCT1 polymorphisms. Condition category: machinery_impairment nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: People who carry a weaker version of the transporter responded less to the drug. organism: Mouse and human, stated per record tissue_or_cell_type: Hepatocytes and whole body experimental_model: Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies limitations: Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing. exposure: Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests evidence_span: {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"} [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558

   Complete structured claim and evidence

10. Intestine-specific knockout of Pen2 impaired the glucose-lowering effects of metformin.

    Intestine-specific Pen2 knockout mice in the 2022 study → Serum glucose concentration source_derived_draftungraded
    Experimental context and source evidence

    availability_state

    machinery_impairment Imported condition classification; unverified.

    evidence_span

    {"source_cache": "artifacts/metformin-research/35197629.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983", "start_char": 0, "end_char": 1549, "text_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983"}

    experimental_model

    Photoactive metformin probe, binding studies, knockouts in mice and C. elegans

    exposure

    Clinically relevant low metformin concentrations; PEN2 knockout and ATP6AP1-binding mutants

    limitations

    A direct binding partner at low dose with a micromolar dissociation constant. Lifespan and fat-content endpoints are model endpoints, not clinical outcomes.

    nutrient_topic

    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

    organism

    Human cells, mouse and C. elegans

    plain_language

    Part of the glucose effect is produced in the gut, not the liver.

    primary_references

    [metformin-p35197629] Low-dose metformin targets the lysosomal AMPK pathway through PEN2. (2022). https://pubmed.ncbi.nlm.nih.gov/35197629/ DOI: 10.1038/s41586-022-04431-8

    tissue_or_cell_type

    Lysosome, liver and intestine

    trigger_kind

    machinery_impairment Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 697–708

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Photoactive metformin probe, binding studies, knockouts in mice and C. elegans · source_derived_draft · unverified_draft

    ### metformin-pen2-null-intestine-glucose Intestine-specific knockout of Pen2 impaired the glucose-lowering effects of metformin. Condition category: machinery_impairment nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Part of the glucose effect is produced in the gut, not the liver. organism: Human cells, mouse and C. elegans tissue_or_cell_type: Lysosome, liver and intestine experimental_model: Photoactive metformin probe, binding studies, knockouts in mice and C. elegans limitations: A direct binding partner at low dose with a micromolar dissociation constant. Lifespan and fat-content endpoints are model endpoints, not clinical outcomes. exposure: Clinically relevant low metformin concentrations; PEN2 knockout and ATP6AP1-binding mutants evidence_span: {"source_cache": "artifacts/metformin-research/35197629.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983", "start_char": 0, "end_char": 1549, "text_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983"} [metformin-p35197629] Low-dose metformin targets the lysosomal AMPK pathway through PEN2. (2022). https://pubmed.ncbi.nlm.nih.gov/35197629/ DOI: 10.1038/s41586-022-04431-8

    Complete structured claim and evidence

11. Ivermectin decreased serum glucose and cholesterol in wild-type mice but not in FXR-null mice.

    Ivermectin → Serum glucose concentration source_derived_draftungraded
    Experimental context and source evidence

    duration

    Not stated here

    evidence_access

    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

    experimental_model

    Wild-type and FXR-null mice

    exposure

    Ivermectin treatment

    limitations

    The null-mouse comparison attributes the metabolic effect to FXR; it does not establish a dose relevant to human antiparasitic use.

    organism

    Wild-type and FXR-null mice

    plain_language

    Ivermectin decreased serum glucose and cholesterol in wild-type mice but not in FXR-null mice.

    primary_references

    The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924

    route

    In vivo

    tissue

    Serum glucose and cholesterol

    Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22) · lines 134–143

    Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## ivermectin-lowers-glucose-through-fxr Ivermectin decreased serum glucose and cholesterol in wild-type mice but not in FXR-null mice. Model/species: Wild-type and FXR-null mice Tissue/system: Serum glucose and cholesterol Exposure: Ivermectin treatment Route: In vivo Duration: Not stated here Limits: The null-mouse comparison attributes the metabolic effect to FXR; it does not establish a dose relevant to human antiparasitic use. Primary reference: The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. (2013). https://pubmed.ncbi.nlm.nih.gov/23728580/ DOI: 10.1038/ncomms2924 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

    Complete structured claim and evidence