Trial reportClinical epigenetics2018
Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals.
Trial report in Clinical epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer.JCI insight · 2020Trial
- Trial
- Causal relationship between epigenetic markers and type 2 diabetes in West African populations: a Mendelian randomisation analysis.Diabetologia · 2026Article
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- Identifying cross-tissue molecular targets of lung function by multi-omics integration analysis from DNA methylation and gene expression of diverse human tissues.BMC genomics · 2025Article
- Harnessing Pharmacomultiomics for Precision Medicine in Diabetes: A Comprehensive Review.Biomedicines · 2025Review
- Causality-driven candidate identification for reliable DNA methylation biomarker discovery.Nature communications · 2025Article
- General anesthesia induces acute cell-free DNA methylation changes in peripheral blood.Journal of thoracic disease · 2024Article
- Differences in DNA Methylation in Genes Involved in Vitamin D Metabolism Are Related to Insulin Requirement in Pregnant Women with Gestational Diabetes Mellitus.International journal of molecular sciences · 2024Article
- Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies.Molecular medicine (Cambridge, Mass.) · 2024Review
- Paternal Use of Metformin During the Sperm Development Period Preceding Conception and Risk for Major Congenital Malformations in Newborns.Annals of internal medicine · 2024Article
- Association of nutritional glycaemic indices with global DNA methylation patterns: results from the Moli-sani cohort.Clinical epigenetics · 2022Article
- Pharmacoepigenetics in type 2 diabetes: is it clinically relevant?Diabetologia · 2022Article
- Identification of novel differentially expressed genes in type 1 diabetes mellitus complications using transcriptomic profiling of UAE patients: a multicenter study.Scientific reports · 2022Article
- Epigenetic Modifications and Non-Coding RNA in Diabetes-Mellitus-Induced Coronary Artery Disease: Pathophysiological Link and New Therapeutic Frontiers.International journal of molecular sciences · 2022Review
- Effect of metformin on the epigenetic age of peripheral blood in patients with diabetes mellitus.Frontiers in genetics · 2022Article
- Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area.International journal of molecular sciences · 2021Review
- Clinical perspectives and concerns of metformin as an anti-aging drug.Aging medicine (Milton (N.S.W)) · 2020Review
- DNA methylation in promoter regions of genes involved in the reproductive and metabolic function of children born to women with PCOS.Epigenetics · 2020Article
- Time course of altered DNA methylation evoked by critical illness and by early administration of parenteral nutrition in the paediatric ICU.Clinical epigenetics · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetformin is a widely prescribed antihyperglycemic agent that has been also associated with multiple therapeutic effects in various diseases, including several types of malignancies. There is growing evidence regarding the contribution of the epigenetic mechanisms in reaching metformin's therapeutic goals; however, the effect of metformin on human cells in vivo is not comprehensively studied. The aim of our study was to examine metformin-induced alterations of DNA methylation profiles in white blood cells of healthy volunteers, employing a longitudinal study design.
resultsTwelve healthy metformin-naïve individuals where enrolled in the study. Genome-wide DNA methylation pattern was estimated at baseline, 10 h and 7 days after the start of metformin administration. The whole-genome DNA methylation analysis in total revealed 125 differentially methylated CpGs, of which 11 CpGs and their associated genes with the most consistent changes in the DNA methylation profile were selected: POFUT2, CAMKK1, EML3, KIAA1614, UPF1, MUC4, LOC727982, SIX3, ADAM8, SNORD12B, VPS8, and several differentially methylated regions as novel potential epigenetic targets of metformin. The main functions of the majority of top-ranked differentially methylated loci and their representative cell signaling pathways were linked to the well-known metformin therapy targets: regulatory processes of energy homeostasis, inflammatory responses, tumorigenesis, and neurodegenerative diseases.
conclusionsHere we demonstrate for the first time the immediate effect of short-term metformin administration at therapeutic doses on epigenetic regulation in human white blood cells. These findings suggest the DNA methylation process as one of the mechanisms involved in the action of metformin, thereby revealing novel targets and directions of the molecular mechanisms underlying the various beneficial effects of metformin.
trial registrationEU Clinical Trials Register, 2016-001092-74. Registered 23 March 2017, https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001092-74/LV .
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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.