ArticleFrontiers in pharmacology2016
Pharmacometabolomic Assessment of Metformin in Non-diabetic, African Americans.
Article in Frontiers in pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control.Nature metabolism · 2026Article
- Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycemic control.bioRxiv : the preprint server for biology · 2025Article
- Analyzing Diabetes Detection and Classification: A Bibliometric Review (2000-2023).Sensors (Basel, Switzerland) · 2024Review
- Bidirectional modulation of TCA cycle metabolites and anaplerosis by metformin and its combination with SGLT2i.Cardiovascular diabetology · 2024Article
- Metformin increases 3-hydroxy medium chain fatty acids in patients with type 2 diabetes: a cross-sectional pharmacometabolomic study.Frontiers in endocrinology · 2024Article
- Pharmacokinetics in Pharmacometabolomics: Towards Personalized Medication.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Metformin modulates the gut microbiome in a mice model of high-fat diet-induced glycolipid metabolism disorder.BMJ open diabetes research & care · 2022Article
- Pharmacokinetic-Pharmacometabolomic Approach in Early-Phase Clinical Trials: A Way Forward for Targeted Therapy in Type 2 Diabetes.Pharmaceutics · 2022Article
- Metabolomic Approaches to Investigate the Effect of Metformin: An Overview.International journal of molecular sciences · 2021Review
- Comparative Evaluation of the Effect of Metformin and Insulin on Gut Microbiota and Metabolome Profiles of Type 2 Diabetic Rats Induced by the Combination of Streptozotocin and High-Fat Diet.Frontiers in pharmacology · 2021Article
- A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol.Canadian journal of kidney health and disease · 2021Article
- Breath Metabolomics Provides an Accurate and Noninvasive Approach for Screening Cirrhosis, Primary, and Secondary Liver Tumors.Hepatology communications · 2020Article
- Obesity Connected Metabolic Changes in Type 2 Diabetic Patients Treated With Metformin.Frontiers in pharmacology · 2020Article
- Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism.Molecular psychiatry · 2018Article
- A Pharmacometabolomic Approach to Predict Response to Metformin in Early-Phase Type 2 Diabetes Mellitus Patients.Molecules (Basel, Switzerland) · 2018Article
- Considerations for automated machine learning in clinical metabolic profiling: Altered homocysteine plasma concentration associated with metformin exposure.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2018Article
- Metabolomics enables precision medicine: "A White Paper, Community Perspective".Metabolomics : Official journal of the Metabolomic SocietyArticle
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Millions of individuals are diagnosed with type 2 diabetes mellitus (T2D), which increases the risk for a plethora of adverse outcomes including cardiovascular events and kidney disease. Metformin is the most widely prescribed medication for the treatment of T2D; however, its mechanism is not fully understood and individuals vary in their response to this therapy. Here, we use a non-targeted, pharmacometabolomics approach to measure 384 metabolites in 33 non-diabetic, African American subjects dosed with metformin. Three plasma samples were obtained from each subject, one before and two after metformin administration. Validation studies were performed in wildtype mice given metformin. Fifty-four metabolites (including 21 unknowns) were significantly altered upon metformin administration, and 12 metabolites (including six unknowns) were significantly associated with metformin-induced change in glucose (q < 0.2). Of note, indole-3-acetate, a metabolite produced by gut microbes, and 4-hydroxyproline were modulated following metformin exposure in both humans and mice. 2-Hydroxybutanoic acid, a metabolite previously associated with insulin resistance and an early biomarker of T2D, was positively correlated with fasting glucose levels as well as glucose levels following oral glucose tolerance tests after metformin administration. Pathway analysis revealed that metformin administration was associated with changes in a number of metabolites in the urea cycle and in purine metabolic pathways (q < 0.01). Further research is needed to validate the biomarkers of metformin exposure and response identified in this study, and to understand the role of metformin in ammonia detoxification, protein degradation and purine metabolic pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.