Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diab Care. 2022;45:2753–86.

Article  CAS  Google Scholar 

Lotfy M, Adeghate J, Kalasz H, Singh J, Adeghate E. Chronic complications of diabetes mellitus: a mini review. Curr Diab Rev. 2017;13:3–10.

Article  CAS  Google Scholar 

Florez JC, Jablonski KA, Taylor A, Mather K, Horton E, White NH, et al. The C allele of ATM rs11212617 does not associate with metformin response in the Diabetes Prevention Program. Diab Care. 2012;35:1864–7.

Article  CAS  Google Scholar 

Fodor A, Cozma A, Suharoschi R, Sitar-Taut A, Roman G. Clinical and genetic predictors of diabetes drug’s response. Drug Metab Rev. 2019;51:408–27.

Article  CAS  Google Scholar 

Wood S, Magliano DJ, Bell JS, Shaw JE, Ilomäki J. Treatment Dynamics in People Who Initiate Metformin or Sulfonylureas for Type 2 Diabetes: A National Cohort Study. Front Pharmacol. 2021;12:794273.

Zhou K, Yee SW, Seiser EL, Van Leeuwen N, Tavendale R, Bennett AJ, et al. Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin. Nat Genet. 2016;48:1055–9.

Article  CAS  PubMed Central  Google Scholar 

Nasykhova YA, Tonyan ZN, Mikhailova AA, Danilova MM, Glotov AS. Pharmacogenetics of type 2 diabetes—progress and prospects. Int J Mol Sci. 2020;21:6842.

Article  CAS  PubMed Central  Google Scholar 

GoDarts, Group UDPS, Wellcome Trust Case Control C, Zhou K, Bellenguez C, Spencer CC, et al. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet. 2011;43:117–20.

Article  Google Scholar 

Li JH, Brenner LN, Kaur V, Figueroa K, Schroeder P, Huerta-Chagoya A, et al. Genome-wide association analysis identifies ancestry-specific genetic variation associated with acute response to metformin and glipizide in SUGAR-MGH. Diabetologia. 2023;66:1260–72.

Article  CAS  PubMed Central  Google Scholar 

Wu B, Yee SW, Xiao S, Xu F, Sridhar SB, Yang M, et al. Genome-Wide Association Study Identifies Pharmacogenomic Variants Associated With Metformin Glycemic Response in African American Patients With Type 2 Diabetes. Diab Care. 2024;47:208–15.

Article  CAS  Google Scholar 

Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong J, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinetics. 2011;50:81–98.

Article  CAS  Google Scholar 

Christensen MMH, Brasch-Andersen C, Green H, Nielsen F, Damkier P, Beck-Nielsen H, et al. The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c. Pharmacogenet genomics. 2011;21:837–50.

Article  CAS  Google Scholar 

Al-Eitan LN, Almomani BA, Nassar AM, Elsaqa BZ, Saadeh NA. Metformin pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 polymorphisms on glycemic control and HbA1c levels. J Personalized Med. 2019;9:17.

Article  Google Scholar 

Jablonski KA, McAteer JB, de Bakker PIW, Franks PW, Pollin TI, Hanson RL, et al. Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. Diabetes. 2010;59:2672–81.

Article  CAS  PubMed Central  Google Scholar 

Dujic T, Zhou K, Yee SW, van Leeuwen N, de Keyser CE, Javorský M, et al. Variants in pharmacokinetic transporters and glycemic response to metformin: a metgen meta‐analysis. Clin Pharmacol Therapeutics. 2017;101:763–72.

Article  CAS  Google Scholar 

Li JH, Szczerbinski L, Dawed AY, Kaur V, Todd JN, Pearson ER, et al. A polygenic score for type 2 diabetes risk is associated with both the acute and sustained response to sulfonylureas. Diabetes. 2021;70:293–300.

Article  CAS  Google Scholar 

Ikram MA, Brusselle GGO, Murad SD, van Duijn CM, Franco OH, Goedegebure A, et al. The Rotterdam Study: 2018 update on objectives, design and main results. Eur J Epidemiol. 2017;32:807–50.

Article  PubMed Central  Google Scholar 

McCarthy S, Das S, Kretzschmar W, Delaneau O, Wood AR, Teumer A, et al. A reference panel of 64,976 haplotypes for genotype imputation. Nat Genet. 2016;48:1279.

Article  CAS  PubMed Central  Google Scholar 

Todd JN, Florez JC. An update on the pharmacogenomics of metformin: progress, problems and potential. Pharmacogenomics. 2014;15:529–39.

Article  CAS  Google Scholar 

Mahajan A, Taliun D, Thurner M, Robertson NR, Torres JM, Rayner NW, et al. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat Genet. 2018;50:1505–13.

Article  CAS  PubMed Central  Google Scholar 

Wang K, Kavousi M, Voortman T, Ikram MA, Ghanbari M, Ahmadizar F. Cardiovascular health, genetic predisposition, and lifetime risk of type 2 diabetes. Eur J Prev Cardiol. 2022;28:1850–7.

Article  Google Scholar 

Belinky F, Nativ N, Stelzer G, Zimmerman S, Iny Stein T, Safran M, et al. PathCards: multi-source consolidation of human biological pathways. Database. 2015;2015:bav006.

Article  PubMed Central  Google Scholar 

Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000;25:25–29.

Article  CAS  PubMed Central  Google Scholar 

Tennant PWG, Murray EJ, Arnold KF, Berrie L, Fox MP, Gadd SC, et al. Use of directed acyclic graphs (DAGs) to identify confounders in applied health research: review and recommendations. Int J Epidemiol. 2020;50:620–32.

Article  PubMed Central  Google Scholar 

Motsinger AA, Ritchie MD. Multifactor dimensionality reduction: an analysis strategy for modelling and detecting gene-gene interactions in human genetics and pharmacogenomics studies. Hum Genomics. 2006;2:1–11.

Article  Google Scholar 

Textor J, van der Zander B, Gilthorpe MS, Liśkiewicz M, Ellison GTH. Robust causal inference using directed acyclic graphs: the R package ‘dagitty. Int J Epidemiol. 2017;45:1887–94.

Google Scholar 

Bates D, Mächler M, Bolker B, Walker S. Fitting Linear Mixed-Effects Models Using lme4. J Stat Softw. 2015;67:1–48.

Article  Google Scholar 

Venables WN, Ripley BD. Modern applied statistics with S-PLUS. New york: Springer Science & Business Media; 2013.

Naja K, El Shamieh S, Fakhoury R. rs622342A>C in SLC22A1 is associated with metformin pharmacokinetics and glycemic response. Drug Metab Pharmacokinet. 2020;35:160–4.

Article  CAS  Google Scholar 

Peng A, Gong C, Xu Y, Liang X, Chen X, Hong W, et al. Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis. Front Public Health. 2023;11:1183879.

Article  PubMed Central  Google Scholar 

Grimes RT, Bennett K, Tilson L, Usher C, Smith SM, Henman MC. Initial therapy, persistence and regimen change in a cohort of newly treated type 2 diabetes patients. Br J Clin Pharmacol. 2015;79:1000–9.

Article  CAS  PubMed Central  Google Scholar 

Kim K, Unni S, Brixner DI, Thomas SM, Olsen CJ, Sterling KL, et al. Longitudinal changes in glycated haemoglobin following treatment intensification after inadequate response to two oral antidiabetic agents in patients with type 2 diabetes. Diab Obes Metab. 2019;21:1725–33.

Article  CAS  Google Scholar 

Martono DP, Heerspink HJL, Hak E, Denig P, Wilffert B. No significant association of type 2 diabetes‐related genetic risk scores with glycated haemoglobin levels after initiating metformin or sulphonylurea derivatives. Diab Obes Metab. 2019;21:2267–73.

Article  CAS  Google Scholar 

Engelbrechtsen L, Andersson E, Roepstorff S, Hansen T, Vestergaard H. Pharmacogenetics and individual responses to treatment of hyperglycemia in type 2 diabetes. Pharmacogenet Genomics. 2015;25:475–84.

Article  CAS  Google Scholar 

Gola D, König IR. Identification of interactions using model-based multifactor dimensionality reduction. In BMC proceedings, vol. 10. BioMed Central; 2016, pp. 135–9.

Christensen MMH, Højlund K, Hother-Nielsen O, Stage TB, Damkier P, Beck-Nielsen H, et al. Endogenous glucose production increases in response to metformin treatment in the glycogen-depleted state in humans: a randomised trial. Diabetologia. 2015;58:2494–502.

Article  CAS  Google Scholar 

Becker ML, Visser LE, van Schaik RH, Hofman A, Uitterlinden AG, Stricker BH. Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response. Pharmacogenet Genomics. 2010;20:38–44.

Article  CAS  Google Scholar 

Thathapudi S, Erukambattu JS, Putcha UK. Multifactor dimensionality reduction analysis for detecting SNP-SNP, SNP-environment interactions associated with polycystic ovarian syndrome among South Indian women. Int J Mol Biol Open Access. 2019;4:59–65.

Article  Google Scholar 

Fullerton MD, Galic S, Marcinko K, Sikk