ArticlePloS one2020
Determination of metformin bio-distribution by LC-MS/MS in mice treated with a clinically relevant paradigm.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
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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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- The effect of Chinese herbal formulas combined with metformin on modulating the gut microbiota in the amelioration of type 2 diabetes mellitus: A systematic review and meta-analysis.Frontiers in endocrinology · 2022Pooled it
- Effect of metformin on pancreatic neuroendocrine tumors of multiple endocrine neoplasia type 1.Journal of neuroendocrinology · 2026Article
- Intracellular Pharmacokinetics of Antidiabetic Drugs: A Focused Narrative Review of Subcellular Distribution (2015-2025).Diseases (Basel, Switzerland) · 2026Review
- Plasma metformin concentration as a determinant of metabolic response in adults with type 1 diabetes: a 1-year prospective observational study.Frontiers in pharmacology · 2026Article
- Development of a Charge-Mediated Disaggregation-Induced Fluorescence Enhancement Platform Using NS-Carbon Dots for Metformin Quantification and Pharmacokinetic Studies.Journal of fluorescence · 2025Article
- Low-dose metformin requires brain Rap1 for its antidiabetic action.Science advances · 2025Article
- Quantitative determination of Metformin in human plasma by UPLC-MS/MS and results of a 12-month pilot study.Scientific reports · 2025Article
- Age-dependent neuroinflammation response to voluntary wheel running and Metformin treatment in the frontal cortex of ovariectomized female mice.Scientific reports · 2025Article
- Comparative Study: Biguanide-, Sulfonamide-, and Natural Agent-Based Interventions in an In Vivo Experimental Diabetes Model.Medicina (Kaunas, Lithuania) · 2025Article
- Recent Advances in Liquid Chromatography-Mass Spectrometry (LC-MS) Applications in Biological and Applied Sciences.Analytical science advances · 2025Review
- Therapeutic effects of metformin on cocaine conditioned place preference and locomotion.Behavioral neuroscience · 2025Article
- Obesity-specific improvement of lung cancer outcomes and immunotherapy efficacy with metformin.Journal of the National Cancer Institute · 2025Article
- Evaluation of systemic and brain pharmacokinetic parameters for repurposing metformin using intravenous bolus administration.The Journal of pharmacology and experimental therapeutics · 2025Article
- A Highly Sensitive UPLC-MS/MS Method for the Quantification of the Organic Cation Transporters' Mediated Metformin Uptake and Its Inhibition in Cells.Molecules (Basel, Switzerland) · 2024Article
- Liver Fibrosis Stages Affect Organic Cation Transporter 1/2 Activities in Hepatitis C Virus-Infected Patients.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Validation and Application of Screen-Printed Microchip for Potentiometric Determination of Metformin Hydrochloride in Tablet Dosage Form.International journal of analytical chemistry · 2024Article
- Green and High Throughput Assay Using 96-Microwell Base to Determine Metformin Hydrochloride in the Tablet Dosage Form.International journal of analytical chemistry · 2024Article
- Quantifying skin permeation of a novel metformin lotion using modified hydrophilic interaction liquid chromatography.Bioanalysis · 2024Article
- The combined treatment with ketogenic diet and metformin slows tumor growth in two mouse models of triple negative breast cancer.Translational medicine communications · 2024Article
- The Combined Treatment with Ketogenic Diet and Metformin Slows Tumor Growth in Two Mouse Models of Triple Negative Breast Cancer.Research square · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Metformin, an anti-diabetes drug, has been recently emerging as a potential "anti-aging" intervention based on its reported beneficial actions against aging in preclinical studies. Nonetheless, very few metformin studies using mice have determined metformin concentrations and many effects of metformin have been observed in preclinical studies using doses/concentrations that were not relevant to therapeutic levels in human. We developed a liquid chromatography-tandem mass spectrometry protocol for metformin measurement in plasma, liver, brain, kidney, and muscle of mice. Young adult male and female C57BL/6 mice were voluntarily treated with metformin of 4 mg/ml in drinking water which translated to the maximum dose of 2.5 g/day in humans. A clinically relevant steady-state plasma metformin concentrations were achieved at 7 and 30 days after treatment in male and female mice. Metformin concentrations were slightly higher in muscle than in plasma, while, ~3 and 6-fold higher in the liver and kidney than in plasma, respectively. Low metformin concentration was found in the brain at ~20% of the plasma level. Furthermore, gender difference in steady-state metformin bio-distribution was observed. Our study established steady-state metformin levels in plasma, liver, muscle, kidney, and brain of normoglycemic mice treated with a clinically relevant dose, providing insight into future metformin preclinical studies for potential clinical translation.
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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.