ArticleMolecular pharmaceutics2015
Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3).
Article in Molecular pharmaceutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.Clinical pharmacology and therapeutics · 2017Pooled it
- Drug-Drug Interaction Between Dihydroartemisinin-Piperaquine and Sulfadoxine-Pyrimethamine During Malaria Chemoprevention in Pregnant Women.Clinical pharmacology and therapeutics · 2025Trial
- Assessing Transporter-Mediated Natural Product-Drug Interactions Via In vitro-In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail.Clinical pharmacology and therapeutics · 2021Trial
- Adverse events associated with drug-related thiamine deficiency: A pharmacovigilance study.JPEN. Journal of parenteral and enteral nutrition · 2026Article
- The Molecular Mechanisms of Metformin's Action on Blood Lipid Profile in Diabetic Patients.International journal of molecular sciences · 2026Review
- Reassessing Transketolase Assays: Methodological Considerations for Detecting Functional Thiamine Deficiency.Annals of the New York Academy of Sciences · 2026Review
- Ginger and Its Purified Major Components Inhibit Clinically Relevant Uptake and Efflux Transporters In Vitro.Pharmaceutics · 2026Article
- Comparison of Metformin PBPK Models Incorporating Placental Transfer to Predict Fetal and Maternal Exposure.CPT: pharmacometrics & systems pharmacology · 2026Article
- Genetic Variants of the Human Thiamine Transporter (International journal of molecular sciences · 2025Article
- Recent Advances on the Role of B Vitamins in Cancer Prevention and Progression.International journal of molecular sciences · 2025Review
- Metformin Effects on SHIP2, AMPKs and Gut Microbiota: Recent Updates on Pharmacology.Current medicinal chemistry · 2025Review
- Substrate transport and drug interaction of human thiamine transporters SLC19A2/A3.Nature communications · 2024Article
- Article
- Rare Diseases Linked to Mutations in Vitamin Transporters Expressed in the Human Blood-Brain Barrier.Clinical pharmacology and therapeutics · 2024Review
- Modulation of Multispecific Transporters byPharmaceutics · 2024Article
- Exome Sequence Data of Eight SLC Transporters Reveal ThatPharmaceuticals (Basel, Switzerland) · 2024Article
- Structural basis of thiamine transport and drug recognition by SLC19A3.Nature communications · 2024Article
- Cross-Sectional Study of Thiamine Deficiency and Its Associated Risks in Emergency Care.The western journal of emergency medicine · 2024Article
- Impact of Drug-Mediated Inhibition of Intestinal Transporters on Nutrient and Endogenous Substrate Disposition…an Afterthought?Pharmaceutics · 2024Review
- Arterial spin labeling perfusion in acute Wernicke encephalopathy: a case series discussion.BJR case reports · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The biguanide metformin is widely used as first-line therapy for the treatment of type 2 diabetes. Predominately a cation at physiological pH's, metformin is transported by membrane transporters, which play major roles in its absorption and disposition. Recently, our laboratory demonstrated that organic cation transporter 1, OCT1, the major hepatic uptake transporter for metformin, was also the primary hepatic uptake transporter for thiamine, vitamin B1. In this study, we tested the reverse, i.e., that metformin is a substrate of thiamine transporters (THTR-1, SLC19A2, and THTR-2, SLC19A3). Our study demonstrated that human THTR-2 (hTHTR-2), SLC19A3, which is highly expressed in the small intestine, but not hTHTR-1, transports metformin (Km = 1.15 ± 0.2 mM) and other cationic compounds (MPP(+) and famotidine). The uptake mechanism for hTHTR-2 was pH and electrochemical gradient sensitive. Furthermore, metformin as well as other drugs including phenformin, chloroquine, verapamil, famotidine, and amprolium inhibited hTHTR-2 mediated uptake of both thiamine and metformin. Species differences in the substrate specificity of THTR-2 between human and mouse orthologues were observed. Taken together, our data suggest that hTHTR-2 may play a role in the intestinal absorption and tissue distribution of metformin and other organic cations and that the transporter may be a target for drug-drug and drug-nutrient interactions.
Indexed as
Identifiers
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.