ArticleDiabetes2015
Mechanism of Altered Metformin Distribution in Nonalcoholic Steatohepatitis.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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
20 citing papers in PubMed, 34 citations in OpenAlex.
- Hepatic exposure of metformin in patients with non-alcoholic fatty liver disease.British journal of clinical pharmacology · 2019Trial
- Increased Metformin Clearance in Overweight and Obese Adolescents: A Pharmacokinetic Substudy of a Randomized Controlled Trial.Paediatric drugs · 2018Trial
- Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.Biology · 2024Review
- Representative Rodent Models for Renal Transporter Alterations in Human Nonalcoholic Steatohepatitis.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Cinchonine, a Potential Oral Small-Molecule Glucagon-Like Peptide-1 Receptor Agonist, Lowers Blood Glucose and Ameliorates Non-Alcoholic Steatohepatitis.Drug design, development and therapy · 2023Article
- Altered cisplatin pharmacokinetics during nonalcoholic steatohepatitis contributes to reduced nephrotoxicity.Acta pharmaceutica Sinica. B · 2021Article
- Drug Transporters in the Kidney: Perspectives on Species Differences, Disease Status, and Molecular Docking.Frontiers in pharmacology · 2021Review
- OATP1B3 Expression and Function is Modulated by Coexpression with OCT1, OATP1B1, and NTCP.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Honokiol Alleviates Methionine-Choline Deficient Diet-Induced Hepatic Steatosis and Oxidative Stress in C57BL/6 Mice by Regulating CFLAR-JNK Pathway.Oxidative medicine and cellular longevity · 2020Article
- Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2019Review
- Hepatic metabolomics reveals that liver injury increases PCB 126-induced oxidative stress and metabolic dysfunction.Chemosphere · 2019Article
- Matrine Protects Against MCD-Induced Development of NASH via Upregulating HSP72 and Downregulating mTOR in a Manner Distinctive From Metformin.Frontiers in pharmacology · 2019Article
- Asking the Right Questions With Animal Models: Methionine- and Choline-Deficient Model in Predicting Adverse Drug Reactions in Human NASH.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Pediatric Cytochrome P450 Activity Alterations in Nonalcoholic Steatohepatitis.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Impaired N-linked glycosylation of uptake and efflux transporters in human non-alcoholic fatty liver disease.Liver international : official journal of the International Association for the Study of the Liver · 2017Article
- Non-alcoholic fatty liver disease (NAFLD) - pathogenesis, classification, and effect on drug metabolizing enzymes and transporters.Drug metabolism reviews · 2017Review
- In vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis mice.Journal of biochemical and molecular toxicology · 2017Article
- Effect of nonalcoholic steatohepatitis on renal filtration and secretion of adefovir.Biochemical pharmacology · 2016Article
- Altered Expression of Transporters, its Potential Mechanisms and Influences in the Liver of Rodent Models Associated with Diabetes Mellitus and Obesity.European journal of drug metabolism and pharmacokinetics · 2016Review
- Age-Related Changes in Hepatic Function: An Update on Implications for Drug Therapy.Drugs & aging · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Metformin is an antihyperglycemic drug that is widely prescribed for type 2 diabetes mellitus and is currently being investigated for the treatment of nonalcoholic steatohepatitis (NASH). NASH is known to alter hepatic membrane transporter expression and drug disposition similarly in humans and rodent models of NASH. Metformin is almost exclusively eliminated through the kidney primarily through active secretion mediated by Oct1, Oct2, and Mate1. The purpose of this study was to determine how NASH affects kidney transporter expression and metformin pharmacokinetics. A single oral dose of [(14)C]metformin was administered to C57BL/6J (wild type [WT]) and diabetic ob/ob mice fed either a control diet or a methionine- and choline-deficient (MCD) diet. Metformin plasma concentrations were slightly increased in the WT/MCD and ob/control groups, whereas plasma concentrations were 4.8-fold higher in ob/MCD mice compared with WT/control. The MCD diet significantly increased plasma half-life and mean residence time and correspondingly decreased oral clearance in both genotypes. These changes in disposition were caused by ob/ob- and MCD diet-specific decreases in the kidney mRNA expression of Oct2 and Mate1, whereas Oct1 mRNA expression was only decreased in ob/MCD mice. These results indicate that the diabetic ob/ob genotype and the MCD disease model alter kidney transporter expression and alter the pharmacokinetics of metformin, potentially increasing the risk of drug toxicity.
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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.