Evidence mapPaperPMID 37233759Full record

ArticleDiabetologia2023

Genome-wide association analysis identifies ancestry-specific genetic variation associated with acute response to metformin and glipizide in SUGAR-MGH.

Josephine H Li, Laura N Brenner, Varinderpal Kaur, Katherine Figueroa, Philip Schroeder, Alicia Huerta-Chagoya, MAGIC Investigators, Diabetes Prevention Program (DPP) Research Group, Miriam S Udler, Aaron Leong and 2 more

Open access · greenAbstract read
In one paragraph

Article in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Common genetic variants nearmedRxiv : the preprint server for health sciences · 2025
    Article
  5. Phenotypic and Genetic Diversity in Diabetes Across Populations.The Journal of clinical endocrinology and metabolism · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Josephine H Li *Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2314-0914
Laura N Brenner *Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Varinderpal Kaur *Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Katherine FigueroaCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Philip SchroederCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9885-7787
Alicia Huerta-ChagoyaCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6218-3904
MAGIC Investigators
Diabetes Prevention Program (DPP) Research Group
Miriam S UdlerCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3824-9162
Aaron LeongCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3248-9547
Josep M MercaderCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8494-3660
Jose C FlorezCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. jcflorez@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-1730-9325
Broad Institute · USHarvard University · USMassachusetts General Hospital · US(Epi)génomique fonctionnelle métabolique et des dysfonctions dans le diabète de type 2 et des maladies associées · FR

Funding

ZD6416 Analgesic--Painful Distal Symmetrical PolyneuropaM01RR001066 · MASSACHUSETTS GENERAL HOSPITAL · 1985 to 2005
$26.1M
PRIMARY PREVENTION TRIAL--DATA COORDINATING CENTERU01DK048489 · GEORGE WASHINGTON UNIVERSITY · 1994 to 2005
$23.7M
PILOT STUDY--SECRETORY TARGETING IN PANCREATIC B CELLSP30DK036836 · JOSLIN DIABETES CENTER · 1986 to 2025
$12.1M
UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · UNIV OF NORTH CAROLINA CHAPEL HILL · 2001 to 2025
$6.9M
TRAINING PROGRAM IN ENDOCRINOLOGY AND DIABETEST32DK007028 · MASSACHUSETTS GENERAL HOSPITAL · 1986 to 2025
$4.2M
MONITORING SOCIAL CHANGE: HEALTH, REPRODUCTION, AGINGR01HD030880 · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · 1994 to 2005
$3.3M
Post-DPP Follow-up-StudyU01DK048377 · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 1994 to 2005
$2.9M
Development of Polygenic Risk Scores for Diabetes and Complications across the Life-Span in Populations of Multiple AncestriesU01HG011723 · BROAD INSTITUTE, INC. · 2025 to 2025
$949k
Elucidating the pharmacogenetics of the response to GLP-1 receptor agonists for type 2 diabetesK23DK131345 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$191k
Mentoring Investigators on the Clinical Translation of Cardiometabolic Genetic DiscoveriesK24HL157960 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$125k
Medical Research Council MC_EX_MR/M009203/1Medical Research Council MC_PC_14089Medical Research Council MC_UU_00007/10Medical Research Council MC_UU_00033/1Medical Research Council MC_UU_00033/3Medical Research Council MR/M009203/1Medical Research Council MR/R010676/1Medical Research Council MR/R024227/1NCATS NIH HHS UL1 TR000170NCRR NIH HHS M01 RR001066NCRR NIH HHS UL1 RR025758NHGRI NIH HHS U01 HG011723NHLBI NIH HHS K24 HL157960NICHD NIH HHS R01 HD030880NIDDK NIH HHS K23 DK114551NIDDK NIH HHS K23 DK125839NIDDK NIH HHS K23 DK131345NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK088214NIDDK NIH HHS R01 GM117163NIDDK NIH HHS R03 DK077675NIDDK NIH HHS T32 DK007028NIDDK NIH HHS U01 DK048377NIDDK NIH HHS U01 DK048489NIEHS NIH HHS P30 ES010126NIGMS NIH HHS R01 GM117163NIH HHS S10 OD026880NIH HHS S10 OD030463
6 · The paper itself

Abstract

aims/hypothesisCharacterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes.

methodsOne thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping Array. Imputation was performed with the TOPMed reference panel. Multiple linear regression using an additive model tested for association between genetic variants and primary endpoints of drug response. In a more focused analysis, we evaluated the influence of 804 unique type 2 diabetes- and glycaemic trait-associated variants on SUGAR-MGH outcomes and performed colocalisation analyses to identify shared genetic signals.

resultsFive genome-wide significant variants were associated with metformin or glipizide response. The strongest association was between an African ancestry-specific variant (minor allele frequency [MAF CONCLUSIONS/

interpretationWe present a well-phenotyped, densely genotyped, multi-ancestry resource to study gene-drug interactions, uncover novel variation associated with response to common glucose-lowering medications and provide insight into mechanisms of action of type 2 diabetes-related variation. DATA AVAILABILITY: The complete summary statistics from this study are available at the Common Metabolic Diseases Knowledge Portal ( https://hugeamp.org ) and the GWAS Catalog ( www.ebi.ac.uk/gwas/ , accession IDs: GCST90269867 to GCST90269899).

Indexed as

Diabetes Mellitus, Type 2MetforminBlood GlucoseGenetic VariationGenome-Wide Association StudyGlipizideGlucoseHumansHypoglycemic AgentsBlood GlucoseGlipizideGlucoseHypoglycemic AgentsMetforminGeneticsGenome-wide association studyGlipizideIncretinMetforminMulti-ancestryPathophysiologyPharmacogeneticsSulfonylureaType 2 diabetes

Identifiers

PMID37233759
PMCPMC10790310
OpenAlexW4378349406

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.