ArticleJournal of pharmacokinetics and pharmacodynamics2015
Prediction and validation of enzyme and transporter off-targets for metformin.
Article in Journal of pharmacokinetics and pharmacodynamics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials.Frontiers in endocrinology · 2022Pooled it
- Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study.Diabetologia · 2019Trial
- Article
- Transcutaneous auricular vagus nerve stimulation to alleviate metformin-associated gastrointestinal adverse events and optimize glycaemic control: a randomized, sham-controlled pilot trial protocol.Frontiers in neuroscience · 2026Article
- A Perspective on the Role of Metformin in Treating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID.ACS pharmacology & translational science · 2025Review
- The Gut Microbiota-Related Antihyperglycemic Effect of Metformin.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Metformin-Associated Gastrointestinal Adverse Events Are Reduced by Probiotics: A Meta-Analysis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- View on Metformin: Antidiabetic and Pleiotropic Effects, Pharmacokinetics, Side Effects, and Sex-Related Differences.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Chronic administration of glucocorticoid receptor ligands increases anxiety-like behavior and selectively increase serotonin transporters in the ventral hippocampus.Brain research · 2023Article
- Metformin alleviates monoamine oxidase-related vascular oxidative stress and endothelial dysfunction in rats with diet-induced obesity.Molecular and cellular biochemistry · 2021Article
- The Hormetic Effect of Metformin: "Less Is More"?International journal of molecular sciences · 2021Review
- Artificial intelligence and machine learning-aided drug discovery in central nervous system diseases: State-of-the-arts and future directions.Medicinal research reviews · 2021Review
- Organic Cation Transporters in the Lung-Current and Emerging (Patho)Physiological and Pharmacological Concepts.International journal of molecular sciences · 2020Review
- Validation strategies for target prediction methods.Briefings in bioinformatics · 2020Review
- Human Copper-Containing Amine Oxidases in Drug Design and Development.Molecules (Basel, Switzerland) · 2020Review
- Alterations of the Predominant Fecal Microbiota and Disruption of the Gut Mucosal Barrier in Patients with Early-Stage Colorectal Cancer.BioMed research international · 2020Article
- Obesity Connected Metabolic Changes in Type 2 Diabetic Patients Treated With Metformin.Frontiers in pharmacology · 2020Article
- Poor short-term glycemic control in patients with type 2 diabetes impairs the intestinal mucosal barrier: a prospective, single-center, observational study.BMC endocrine disorders · 2019Observational
- Prenatal metformin exposure or organic cation transporter 3 knock-out curbs social interaction preference in male mice.Pharmacological research · 2019Article
- Pharmacokinetics of metformin in patients with gastrointestinal intolerance.Diabetes, obesity & metabolism · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Metformin, an established first-line treatment for patients with type 2 diabetes, has been associated with gastrointestinal (GI) adverse effects that limit its use. Histamine and serotonin have potent effects on the GI tract. The effects of metformin on histamine and serotonin uptake were evaluated in cell lines overexpressing several amine transporters (OCT1, OCT3 and SERT). Metformin inhibited histamine and serotonin uptake by OCT1, OCT3 and SERT in a dose-dependent manner, with OCT1-mediated amine uptake being most potently inhibited (IC50 = 1.5 mM). A chemoinformatics-based method known as Similarity Ensemble Approach predicted diamine oxidase (DAO) as an additional intestinal target of metformin, with an E-value of 7.4 × 10(-5). Inhibition of DAO was experimentally validated using a spectrophotometric assay with putrescine as the substrate. The Ki of metformin for DAO was measured to be 8.6 ± 3.1 mM. In this study, we found that metformin inhibited intestinal amine transporters and DAO at concentrations that may be achieved in the intestine after therapeutic doses. Further studies are warranted to determine the relevance of these interactions to the adverse effects of metformin on the gastrointestinal tract.
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What OpenQuestion holds
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.