ArticleDiabetologia2023
Genome-wide association analysis identifies ancestry-specific genetic variation associated with acute response to metformin and glipizide in SUGAR-MGH.
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.
What it found
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Disentangling Sex Differences in Sulfonylurea Drug Response With Genome-Wide Association Studies in Individuals With Type 2 Diabetes.Clinical pharmacology and therapeutics · 2026Article
- Interplay between obesity-associated insulin resistance and immune system through the lens of evolutionary medicine.Molecular metabolism · 2026Review
- Race, ethnicity and ancestry in global diabetes research: grappling with complexity to advance equity and scientific integrity - a narrative review and viewpoint.Diabetologia · 2025Review
- Common genetic variants nearmedRxiv : the preprint server for health sciences · 2025Article
- Phenotypic and Genetic Diversity in Diabetes Across Populations.The Journal of clinical endocrinology and metabolism · 2025Review
- Clinical use of polygenic scores in type 2 diabetes: challenges and possibilities.Diabetologia · 2025Review
- Effects and interaction of single nucleotide polymorphisms at the pharmacokinetic/pharmacodynamic site: insights from the Rotterdam study into metformin clinical response and dose titration.The pharmacogenomics journal · 2024Article
- Initial Insights into the Genetic Variation Associated with Metformin Treatment Failure in Youth with Type 2 Diabetes.Pediatric diabetes · 2023Article
- Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
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).
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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 Socratic graph.