ArticleNature genetics2016
Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin.
Open access · greenAbstract read
In one paragraph
Article in Nature genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed, 6 pooled it
11.5field-weighted citation impact, top 1% 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
138 citing papers in PubMed, 6 syntheses or guidelines pooled it, 226 citations in OpenAlex.
- Genome-Wide Association Study Identifies Pharmacogenomic Variants Associated With Metformin Glycemic Response in African American Patients With Type 2 Diabetes.Diabetes care · 2024Pooled it
- Identification of Novel Intronic SNPs in Transporter Genes Associated with Metformin Side Effects.Genes · 2023Pooled it
- A resource for integrated genomic analysis of the human liver.Scientific reports · 2022Pooled it
- Genomic editing of metformin efficacy-associated genetic variants in SLC47A1 does not alter SLC47A1 expression.Human molecular genetics · 2022Pooled it
- Genome-Wide Meta-analysis Identifies Genetic Variants Associated With Glycemic Response to Sulfonylureas.Diabetes care · 2021Pooled it
- Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.Clinical pharmacology and therapeutics · 2017Pooled it
- Genetic Variants inDiabetes · 2018Trial
- Disentangling Sex Differences in Sulfonylurea Drug Response With Genome-Wide Association Studies in Individuals With Type 2 Diabetes.Clinical pharmacology and therapeutics · 2026Article
- Article
- Early identification of suboptimal responders to metformin in type 2 diabetes using long-term real-world HbA1c trajectories.medRxiv : the preprint server for health sciences · 2026Article
- Association of the FTO rs9939609 variant with glycemic control based on fasting glucose.BMC research notes · 2026Article
- Article
- Evaluating the Impact of Putative Metformin Targets on Cancer Outcomes: A Drug-Target Mendelian Randomization Study.Diabetes, obesity & metabolism · 2026Article
- Metformin beyond Glycemic Control: New Mechanistic Insights and Expanding Therapeutic Horizons.Diabetes & metabolism journal · 2026Review
- Interplay between obesity-associated insulin resistance and immune system through the lens of evolutionary medicine.Molecular metabolism · 2026Review
- Separating the genetics of disease, treatment, and treatment response using graphical modeling and large-scale electronic health records.medRxiv : the preprint server for health sciences · 2026Article
- A comparative anti-proliferative and immunomodulatory analysis in wild and lab-acclimatized seaweed extracts unravel the functional biopotentials of Acrosiphonia orientalis.Scientific reports · 2026Article
- Transporter gene variants influencing metformin pharmacokinetics and pharmacodynamics common in European populations: a pharmacogenetic narrative review.Frontiers in pharmacology · 2026Review
- Optimization of nursing strategies for semaglutide treatment in overweight type 2 diabetes based on gene polymorphism.Frontiers in clinical diabetes and healthcare · 2026Article
- Review
78 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
51 authors at 16 institutions in 7 countries.
Kaixin Zhou *School of Medicine, University of Dundee, Dundee, UK.
Sook Wah Yee *Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
Eric L SeiserDivision of Pharmacotherapy and Experimental Therapeutics, Center for Pharmacogenomics and Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
Nienke van LeeuwenDepartment of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
Roger TavendaleSchool of Medicine, University of Dundee, Dundee, UK.
Amanda J BennettOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Christopher J GrovesOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Ruth L ColemanDiabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Amber A van der HeijdenDepartment of General Practice, EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.
Joline W BeulensDepartment of Epidemiology and Biostatistics, EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.
Catherine E de KeyserDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Linda ZaharenkoLatvian Genome Data Base (LGDB), Riga, Latvia.
Daniel M RotroffBioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA.
Mattijs OutTreant Zorggroep, Location Bethesda, Hoogeveen, the Netherlands.
Kathleen A JablonskiBiostatistics Center, George Washington University, Rockville, Maryland, USA.
Ling ChenDiabetes Unit and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
Martin JavorskýFaculty of Medicine, Šafárik University, Košice, Slovakia.
Jozef ŽidzikFaculty of Medicine, Šafárik University, Košice, Slovakia.
Albert M LevinDepartment of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA.
L Keoki WilliamsCenter for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan, USA.
Tanja DujicSchool of Medicine, University of Dundee, Dundee, UK.
Sabina SemizFaculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
Michiaki KuboRIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
Huan-Chieh ChienDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
Shiro MaedaDepartment of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
John S WitteDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Longyang WuDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Ivan TkáčFaculty of Medicine, Šafárik University, Košice, Slovakia.
Adriaan KooyTreant Zorggroep, Location Bethesda, Hoogeveen, the Netherlands.
Ron H N van SchaikDepartment of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Coen D A StehouwerDepartment of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands.
Lisa LogieSchool of Medicine, University of Dundee, Dundee, UK.
MetGen Investigators
DPP Investigators
ACCORD Investigators
Calum SutherlandSchool of Medicine, University of Dundee, Dundee, UK.
Janis KlovinsLatvian Genome Data Base (LGDB), Riga, Latvia.
Valdis PiragsLatvian Biomedical Research and Study Centre, Riga, Latvia.
Albert HofmanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Bruno H StrickerDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Alison A Motsinger-ReifBioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA.
Michael J WagnerCenter for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Federico InnocentiDivision of Pharmacotherapy and Experimental Therapeutics, Center for Pharmacogenomics and Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
Leen M 't HartDepartment of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
Rury R HolmanDiabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Mark I McCarthyOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Monique M HeddersonDivision of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Colin N A PalmerSchool of Medicine, University of Dundee, Dundee, UK.
Jose C FlorezDiabetes Unit and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
Kathleen M GiacominiDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
Ewan R PearsonSchool of Medicine, University of Dundee, Dundee, UK.
University of Dundee · GBUniversity of North Carolina at Chapel Hill · USUniversity of California, San Francisco · USLatvian Biomedical Research and Study Centre · LVNorth Carolina State University · USHenry Ford Health System · USUniversity of Pavol Jozef Šafárik · SKUniversity of Sarajevo · BAErasmus MC · NLKaiser Permanente · USLeiden University Medical Center · NLUniversity of Oxford · GBAmsterdam Public Health · NLBroad Institute · USCentre for Human Genetics · GBGeorge Washington University · US
Funding
PRIMARY PREVENTION TRIAL--DATA COORDINATING CENTERU01DK048489 · NIDDK · GEORGE WASHINGTON UNIVERSITY · PI JABLONSKI, KATHLEEN ANN, TEMPROSA, MARINELLA · 1994 to 2021
$84.8MVector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Sakeneh Zraika · 1986 to 2026
$41.4MA Resource for Genetic Epidemiology Research in Adult Health and AgingRC2AG036607 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI RISCH, NEIL J., SCHAEFER, CATHERINE ANN · 2009 to 2010
$24.8MPharmacogenomics of Membrane TransportersU19GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YEE, SOOK WAH · 2010 to 2014
$16.3MPost-DDP Follow-up StudyU01DK048413 · NIDDK · UNIVERSITY OF WASHINGTON · PI KAHN, STEVEN EMANUEL · 1994 to 2021
$13.7MPRIMARY PREVENTION TRIAL (DPT-2)U01DK048397 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI NATHAN, DAVID M · 1994 to 2021
$12.0MNIDDM PRIMARY PREVENTION TRIAL (DPT 2)U01DK048404 · NIDDK · ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS · PI LAFERRERE, BLANDINE B · 1994 to 2021
$11.6MNIDDM PRIMARY PREVENTION TRIALU01DK048412 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VENDITTI, ELIZABETH MARY · 1994 to 2021
$11.4MPRIMARY PREVENTION TRIALU01DK048387 · NIDDK · MEDSTAR RESEARCH INSTITUTE · PI MAGEE, MICHELLE FISCHMANN · 1994 to 2022
$11.1MTITLE OMITTEDU01DK048349 · NIDDK · YESHIVA UNIVERSITY · PI CRANDALL, JILL P · 1994 to 2021
$11.0MPRIMARY PREVENTION TRIALU01DK048443 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI WATSON, KAROL E · 1994 to 2021
$10.2MPost-DPP Follow-up StudyU01DK048375 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI DABELEA, DANA · 1994 to 2022
$10.0MDiabetes UK 10/0004063NHLBI NIH HHS R01 HL110380NHLBI NIH HHS R01 HL118267NIAID NIH HHS R01 AI079139NIA NIH HHS RC2 AG036607NIDDK NIH HHS P30 DK017047NIDDK NIH HHS R01 DK064695NIDDK NIH HHS R01 DK072041NIDDK NIH HHS R01 DK078907NIDDK NIH HHS U01 DK048349NIDDK NIH HHS U01 DK048375NIDDK NIH HHS U01 DK048377NIDDK NIH HHS U01 DK048380NIDDK NIH HHS U01 DK048381NIDDK NIH HHS U01 DK048387NIDDK NIH HHS U01 DK048397NIDDK NIH HHS U01 DK048400NIDDK NIH HHS U01 DK048404NIDDK NIH HHS U01 DK048406NIDDK NIH HHS U01 DK048407NIDDK NIH HHS U01 DK048411NIDDK NIH HHS U01 DK048412NIDDK NIH HHS U01 DK048413NIDDK NIH HHS U01 DK048434NIDDK NIH HHS U01 DK048437NIDDK NIH HHS U01 DK048443NIDDK NIH HHS U01 DK048468NIDDK NIH HHS U01 DK048485NIDDK NIH HHS U01 DK048489NIDDK NIH HHS U01 DK048514NIDDK NIH HHS U01 DK085545NIGMS NIH HHS R01 GM117163NIGMS NIH HHS U19 GM061390Wellcome Trust 084727/Z/08/ZWellcome Trust 085475/B/08/ZWellcome Trust 085475/Z/08/ZWellcome Trust 090532Wellcome Trust 092272Wellcome Trust 098381Wellcome Trust 102820Wellcome Trust 102820/Z/13/Z
Abstract
Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 × 10(-14)) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. Among obese individuals, C-allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes. This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550 mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine.
Indexed as
Quantitative Trait, HeritableBlood GlucoseBody Mass IndexDiabetes Mellitus, Type 2Genome-Wide Association StudyGlucose Transporter Type 2Glycated HemoglobinHumansHypoglycemic AgentsMetforminPolymorphism, Single NucleotideWhite PeopleBlood GlucoseGlucose Transporter Type 2Glycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic AgentsMetforminSLC2A2 protein, human
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