Trial reportPloS one2018
A non-linear pharmacokinetic-pharmacodynamic relationship of metformin in healthy volunteers: An open-label, parallel group, randomized clinical study.
Trial report in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02712619 (An Open-label, Parallel Group Clinical Trial to Investigate the Pharmacokinetics/Pharmacodynamics of 250/1000 mg of Metformin IR After Oral Administration in Healthy Male Volunteers), which is not on this map. Cited by 16 papers.
What it found
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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.
An Open-label, Parallel Group Clinical Trial to Investigate the Pharmacokinetics/Pharmacodynamics of 250/1000 mg of Metformin IR After Oral Administration in Healthy Male Volunteers
Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Effects of vancomycin-induced gut microbiome alteration on the pharmacodynamics of metformin in healthy male subjects.Clinical and translational science · 2021Trial
- Trial
- Frequency of Polymorphisms inInternational journal of molecular sciences · 2025Article
- Quantitative Contributions of Hepatic and Renal Organic Cation Transporters to the Clinical Pharmacokinetic Cimetidine-Metformin Interaction.Clinical pharmacology and therapeutics · 2025Article
- Quantitative determination of Metformin in human plasma by UPLC-MS/MS and results of a 12-month pilot study.Scientific reports · 2025Article
- Comparative Study: Biguanide-, Sulfonamide-, and Natural Agent-Based Interventions in an In Vivo Experimental Diabetes Model.Medicina (Kaunas, Lithuania) · 2025Article
- Pharmacokinetic and Pharmacodynamic Interaction of Metformin and Ojeok-san in Healthy Volunteers.Drug design, development and therapy · 2025Article
- N-acetyltransferase Gene Variants Involved in Pediatric Idiosyncratic Drug-Induced Liver Injury.Biomedicines · 2024Article
- Selection of clinically relevant drug concentrations for in vitro studies of candidates drugs for cancer repurposing: a proposal.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Effects of plateau hypoxia on population pharmacokinetics and pharmacodynamics of metformin in patients with Type 2 diabetes.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Article
- Metformin: A Prospective Alternative for the Treatment of Chronic Pain.Frontiers in pharmacology · 2020Review
- Mechanisms of action of metformin with special reference to cardiovascular protection.Diabetes/metabolism research and reviews · 2019Review
- Drugs to Control Diabetes During Pregnancy.Clinics in perinatology · 2019Review
- Commentary: Lactate-Induced Glucose Output Is Unchanged by Metformin at a Therapeutic Concentration-A Mass Spectrometry Imaging Study of the Perfused Rat Liver.Frontiers in pharmacology · 2019Article
- Does the antidiabetic drug metformin affect embryo development and the health of brown trout (Environmental sciences Europe · 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
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe aim of this study was to explore the pharmacokinetic-pharmacodynamic (PK-PD) relationship of metformin on glucose levels after the administration of 250 mg and 1000 mg of metformin in healthy volunteers.
methodsA total of 20 healthy male volunteers were randomized to receive two doses of either a low dose (375 mg followed by 250 mg) or a high dose (1000 mg followed by 1000 mg) of metformin at 12-h intervals. The pharmacodynamics of metformin was assessed using oral glucose tolerance tests before and after metformin administration. The PK parameters after the second dose were evaluated through noncompartmental analyses. Four single nucleotide polymorphisms in MATE1, MATE2-K, and OCT2 were genotyped, and their effects on PK characteristics were additionally evaluated.
resultsThe plasma exposure of metformin increased as the metformin dose increased. The mean values for the area under the concentration-time curve from dosing to 12 hours post-dose (AUC0-12h) were 3160.4 and 8808.2 h·μg/L for the low- and high-dose groups, respectively. Non-linear relationships were found between the glucose-lowering effect and PK parameters with a significant inverse trend at high metformin exposure. The PK parameters were comparable among subjects with the genetic polymorphisms.
conclusionsThis study showed a non-linear PK-PD relationship on plasma glucose levels after the administration of metformin. The inverse relationship between systemic exposure and the glucose-lowering effect at a high exposure indicates a possible role for the intestines as an action site for metformin.
trial registrationClinicalTrials.gov NCT02712619.
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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.