Trial reportPharmacogenetics and genomics2011
The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c.
Trial report in Pharmacogenetics and genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 131 papers, 5 of them syntheses 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.
Impact of OCT1 Genotype and OCT1 Inhibiting Drugs on an Individual's Tolerance of Metformin
Metformin Pharmacology in Human Cancers
Who cites it
131 citing papers in PubMed, 5 syntheses or guidelines pooled it, 256 citations in OpenAlex.
- Influence of Solute Carrier Family 22 Member 1 (Current diabetes reviews · 2024Pooled it
- Genomic editing of metformin efficacy-associated genetic variants in SLC47A1 does not alter SLC47A1 expression.Human molecular genetics · 2022Pooled it
- Metformin Can Be Safely Used in Patients Exposed to Contrast Media: A Systematic Review and Meta-Analysis.Cardiology · 2022Pooled it
- Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.Clinical pharmacology and therapeutics · 2017Pooled it
- Therapeutic Concentrations of Metformin: A Systematic Review.Clinical pharmacokinetics · 2016Pooled it
- Trial
- Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance.Journal of clinical pharmacology · 2017Trial
- 18F-FDG uptake in the colon is modulated by metformin but not associated with core body temperature and energy expenditure.PloS one · 2017Trial
- The effect of dipyridamole on the pharmacokinetics of metformin: a randomized crossover study in healthy volunteers.European journal of clinical pharmacology · 2016Trial
- Endogenous glucose production increases in response to metformin treatment in the glycogen-depleted state in humans: a randomised trial.Diabetologia · 2015Trial
- Steady-state pharmacokinetics of metformin is independent of the OCT1 genotype in healthy volunteers.European journal of clinical pharmacology · 2015Trial
- A pharmacogenetic association between a variation in calpain 10 (CAPN10) gene and the response to metformin treatment in patients with type 2 diabetes.European journal of clinical pharmacology · 2015 · on this mapTrial
- Gene-Guided Therapy in Type 2 Diabetes Mellitus: An Integrative Review of the Pharmacogenetics of Metformin and Sodium-Glucose Cotransporter-2 Inhibitors.Endocrinology, diabetes & metabolism · 2026Review
- Metformin Pharmacogenetics in Heart Failure Patients with Reduced Ejection Fraction: Impact on Metformin and Growth Differentiation Factor-15 Plasma Levels.Clinical pharmacokinetics · 2026Article
- Untargeted Metabolomics Identifies N-Lactoyl-Amino Acids as Dose-Responsive Plasma Biomarkers of Metformin Adherence in Type 2 Diabetes.Clinical pharmacology and therapeutics · 2026Article
- PMAT enhances sexual dimorphism of fear behaviors and facilitates female mice's generalized contextual fear extinction.Frontiers in neuroscience · 2026Article
- Transporter gene variants influencing metformin pharmacokinetics and pharmacodynamics common in European populations: a pharmacogenetic narrative review.Frontiers in pharmacology · 2026Review
- Pharmacogenetics and Molecular Ancestry ofPharmaceuticals (Basel, Switzerland) · 2025Article
- PEGylated liposomal metformin overcomes pharmacokinetic barriers to trigger potent mitochondrial disruption and cell cycle arrest in hepatocellular carcinoma.Scientific reports · 2025Article
- Clinical use of polygenic scores in type 2 diabetes: challenges and possibilities.Diabetologia · 2025Review
71 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe aim of this study was to evaluate the effect of genetic variations in OCT1, OCT2, MATE1, MATE 2, and PMAT on the trough steady-state plasma concentration of metformin and hemoglobin A1c (Hb1Ac).
methodThe South Danish Diabetes Study was a 2 x 2 x 2 factorial, prospective, randomized, double-blind, placebo-controlled, multicentre study. One hundred and fifty-nine patients received 1 g of metformin, twice daily continuously, and 415 repeated plasma metformin measurements were obtained after 3, 6, and 9 months of treatment.
resultsThe mean trough steady-state metformin plasma concentration was estimated to be 576 ng/ml (range, 54–4133 ng/ml, p = 0.55) and correlated to the number of reduced function alleles in OCT1 (none, one or two: 642, 542, 397 ng/ml; P = 0.001). The absolute decrease in Hb1Ac both initially and long term was also correlated to the number of reduced function alleles in OCT1 resulting in diminished pharmacodynamic effect of metformin after 6 and 24 months.
conclusionIn a large cohort of type 2 diabetics, we either confirm or show for the first time: (a) an enormous (80-fold) variability in trough steady-state metformin plasma concentration, (b) OCT1 activity affects metformin steady-state pharmacokinetics, and (c) OCT1 genotype has a bearing on HbA1c during metformin treatment.
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.