Observational studyDiabetes care2015
Effects of metformin on metabolite profiles and LDL cholesterol in patients with type 2 diabetes.
Registry-linked trialOpen access · bronzeAbstract readObservational Study
In one paragraph
Observational study in Diabetes care, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03039075 (Comparison of Metformin Hydrochloride Sustained-release Tablet), which is not on this map. Cited by 71 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 2 pooled it
6.2field-weighted citation impact, top 3% of its field
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.
Comparison of Metformin Hydrochloride Sustained-release Tablet (DuLeNing) and Glucophage in Patients With Type 2 Diabetes
PMID 26285584other papers from this trial
Open the trial in the graphWho cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 148 citations in OpenAlex.
- Efficacy of Metformin in Prevention of Glucocorticoid-Induced Hyperglycemia in Patients Without Diabetes: A Meta-Analysis.Endocrinology, diabetes & metabolism · 2026Pooled it
- Antiproliferative Mechanisms of Metformin in Breast Cancer: A Systematic Review of the Literature.International journal of molecular sciences · 2024Pooled it
- Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial.Scientific reports · 2025Trial
- Short-term Metformin Protects Against Glucocorticoid-Induced Toxicity in Healthy Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial.Diabetes care · 2025 · on this mapTrial
- Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.Diabetes & metabolism journal · 2024Trial
- Effects of Metformin on Left Ventricular Size and Function in Hypertensive Patients with Type 2 Diabetes Mellitus: Results of a Randomized, Controlled, Multicenter, Phase IV Trial.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2020Trial
- Comparing the effects of ipragliflozin versus metformin on visceral fat reduction and metabolic dysfunction in Japanese patients with type 2 diabetes treated with sitagliptin: A prospective, multicentre, open-label, blinded-endpoint, randomized controlled study (PRIME-V study).Diabetes, obesity & metabolism · 2019Trial
- Brain education-based meditation for patients with hypertension and/or type 2 diabetes: A pilot randomized controlled trial.Medicine · 2019Trial
- Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials.Molecular psychiatry · 2016Trial
- Distinct metabolomic profiles in lean and non-lean polyendocrine metabolic ovarian syndrome.Journal of assisted reproduction and genetics · 2026Article
- The Molecular Mechanisms of Metformin's Action on Blood Lipid Profile in Diabetic Patients.International journal of molecular sciences · 2026Review
- Integrative Metabolomics of Targeted and Nontargeted Analyses in T2D Progression.Diabetes care · 2026Article
- Metformin Ameliorates Cognitive Deficits and Neuroinflammation in a Mouse Model of Familial Hypercholesterolemia.Neurochemical research · 2026Article
- Causal knowledge graph analysis identifies adverse drug effects.Bioinformatics (Oxford, England) · 2026Article
- Evaluation and AI-powered prediction of the efficacy of alirocumab use among patients with cardiovascular disease.Frontiers in pharmacology · 2026Article
- Metformin Increases Serum Isthmin-1 Levels and Lowers Low-Density Lipoprotein: Potential Implications for Lipid Metabolism in T2DM.Medicina (Kaunas, Lithuania) · 2025Article
- Metabolomics uncovers the diabetes metabolic network: from pathophysiological mechanisms to clinical applications.Frontiers in endocrinology · 2025Review
- Bidirectional modulation of TCA cycle metabolites and anaplerosis by metformin and its combination with SGLT2i.Cardiovascular diabetology · 2024Article
- Metformin role in Parkinson's disease: a double-sword effect.Molecular and cellular biochemistry · 2024Review
- Effects of long-term metformin administration associated with high-intensity interval training on physical performance, glycogen concentration, GLUT-4 content, and NMR-based metabolomics in healthy rats.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
48 authors at 19 institutions in 5 countries.
Tao XuResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Stefan BrandmaierResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Ana C MessiasInstitute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Christian HerderInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany.
Harmen H M DraismaDepartment of Biological Psychology, Faculty of Psychology and Education, VU University Amsterdam, Amsterdam, the Netherlands EMGO Institute for Health and Care Research, Amsterdam, the Netherlands Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
Ayse DemirkanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Zhonghao YuResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Janina S RiedInstitute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
Toomas HallerEstonian Genome Center, University of Tartu, Tartu, Estonia.
Margit HeierInstitute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Monica CampillosInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Gisela FoboInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Renee StarkInstitute of Health Economics and Health Care Management, Helmholtz Zentrum München, Neuherberg, Germany.
Christina HolzapfelElse Kroener-Fresenius-Center for Nutritional Medicine, Faculty of Medicine, Technische Universität München, Munich, Germany.
Jonathan AdamResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Shen ChiResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Markus RotterResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Tommaso PanniInstitute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Anne S QuanteInstitute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
Ying HeShanghai Center for Bioinformation Technology, Shanghai, China Bioinformatics Center, Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Cornelia PrehnInstitute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.
Werner Roemisch-MarglInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Gabi KastenmüllerInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Gonneke WillemsenDepartment of Biological Psychology, Faculty of Psychology and Education, VU University Amsterdam, Amsterdam, the Netherlands EMGO Institute for Health and Care Research, Amsterdam, the Netherlands.
René PoolDepartment of Biological Psychology, Faculty of Psychology and Education, VU University Amsterdam, Amsterdam, the Netherlands EMGO Institute for Health and Care Research, Amsterdam, the Netherlands.
Katarina KasaDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Ko Willems van DijkDepartment of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Thomas HankemeierFaculty of Science, Leiden Academic Centre for Drug Research, Analytical BioSciences, the Netherlands.
Christa MeisingerInstitute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Barbara ThorandInstitute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Andreas RueppInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Martin Hrabé de AngelisInstitute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, Germany Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Freising, Germany German Center for Diabetes Research, Neuherberg, Germany.
Yixue LiShanghai Center for Bioinformation Technology, Shanghai, China Bioinformatics Center, Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
H-Erich WichmannInstitute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany Institute of Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany.
Bernd StratmannHeart and Diabetes Center NRW, Diabetes Center, Ruhr-University Bochum, Bad Oeynhausen, Germany.
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
Andres MetspaluEstonian Genome Center, University of Tartu, Tartu, Estonia.
Christian GiegerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.
Karsten SuhreInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany Faculty of Biology, Ludwig-Maximilians-Universität, Planegg-Martinsried, Germany Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.
Jerzy AdamskiInstitute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Freising, Germany German Center for Diabetes Research, Neuherberg, Germany.
Thomas IlligResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
Wolfgang RathmannInstitute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
Michael RodenInstitute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany German Center for Diabetes Research, Düsseldorf, Germany Department of Endocrinology and Diabetology, Medical Faculty, Düsseldorf, Germany.
Annette PetersResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany German Center for Diabetes Research, Neuherberg, Germany Department of Environmental Health, Harvard School of Public Health, Boston, MA.
Cornelia M van DuijnNeuroscience Campus Amsterdam, Amsterdam, the Netherlands Center for Medical Systems Biology, Leiden, the Netherlands.
Dorret I BoomsmaDepartment of Biological Psychology, Faculty of Psychology and Education, VU University Amsterdam, Amsterdam, the Netherlands EMGO Institute for Health and Care Research, Amsterdam, the Netherlands.
Thomas MeitingerInstitute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany Institute of Human Genetics, Technische Universität München, Munich, Germany.
Rui Wang-SattlerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany German Center for Diabetes Research, Neuherberg, Germany rui.wang-sattler@helmholtz-muenchen.de.
Helmholtz Zentrum München · DEMedizinische Hochschule Hannover · DEInstitute of Bioinformatics and Systems Biology · DEDeutsches Diabetes-Zentrum e.V. · DELudwig-Maximilians-Universität München · DETechnical University of Munich · DEAmsterdam Neuroscience · NLAmsterdam Public Health · NLCentre for Human Drug Research · NLCentre for Medical Systems Biology · NLErasmus MC · NLFresenius (Germany) · DEGerman Center for Diabetes Research · DEHeinrich Heine University Düsseldorf · DERuhr University Bochum · DEShanghai Center For Bioinformation Technology · CNShanghai Institutes for Biological Sciences · CNUniversity of Tartu · EEWeill Cornell Medical College in Qatar · QA
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveMetformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin. RESEARCH DESIGN AND
methodsWe analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131 metabolites in fasting serum samples and used multivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metformin-associated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways.
resultsWe found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years' follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target.
conclusionsOur results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease.
Indexed as
AgedCholesterol, LDLCross-Sectional StudiesDelta-5 Fatty Acid DesaturaseDiabetes Mellitus, Type 2Diabetic AngiopathiesFastingFatty Acid DesaturasesFemaleGenomicsGenotypeHumansHypoglycemic AgentsLipid MetabolismMaleMetabolomicsCholesterol, LDLDelta-5 Fatty Acid DesaturaseFADS1 protein, humanFADS2 protein, humanFatty Acid DesaturasesHypoglycemic AgentsMetformin
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Texttitle and abstract
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Registered trials
NCT03039075ClinicalTrials.gov
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.