2018
Association of Hemoglobin A1c Levels With Use of Sulfonylureas, Dipeptidyl Peptidase 4 Inhibitors, and Thiazolidinediones in Patients With Type 2 Diabetes Treated With Metformin
Vashisht R, Jung K, Schuler A, Banda J, Park R, Jin S, Li L, Dudley J, Johnson K, Shervey M, Xu H, Wu Y, Natrajan K, Hripcsak G, Jin P, Van Zandt M, Reckard A, Reich C, Weaver J, Schuemie M, Ryan P, Callahan A, Shah N. Association of Hemoglobin A1c Levels With Use of Sulfonylureas, Dipeptidyl Peptidase 4 Inhibitors, and Thiazolidinediones in Patients With Type 2 Diabetes Treated With Metformin. JAMA Network Open 2018, 1: e181755. PMID: 30646124, PMCID: PMC6324274, DOI: 10.1001/jamanetworkopen.2018.1755.Peer-Reviewed Original ResearchConceptsDPP-4 inhibitorsDipeptidyl peptidase-4 inhibitorsFirst-line therapyPeptidase-4 inhibitorsSecond-line drugsType 2 diabetesMyocardial infarctionEye disordersKidney disordersDrug classesSecond-line treatment choiceTotal hemoglobinObservational Health Data SciencesSecond-line treatment optionNew-user cohort studyEffectiveness of sulfonylureasSecond-line treatmentHemoglobin A1c levelsUse of sulfonylureasHealth Data SciencesLarge international studyElectronic medical recordsRoutine medical practiceInsurance claims dataCohort study
2016
Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology
Hart T, Dider S, Han W, Xu H, Zhao Z, Xie L. Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology. Scientific Reports 2016, 6: 20441. PMID: 26841718, PMCID: PMC4740793, DOI: 10.1038/srep20441.Peer-Reviewed Original ResearchConceptsPrecision anti-cancer therapyMolecular basisAnti-cancer therapyStructural systems pharmacologyProtein-protein interactionsDrug target identificationNetwork biology analysisMolecular targetsInteractomic dataGenetic interactionsStructural proteomeGenetic networksKey molecular targetsPhenotypic responsesKinase targetsBiology analysisCancer mutationsPleiotropic effectsAnti-cancer effectsNetwork biomarkersTarget identificationGenetic biomarkersSystems pharmacology approachKey nodesTarget
2015
Deciphering Signaling Pathway Networks to Understand the Molecular Mechanisms of Metformin Action
Sun J, Zhao M, Jia P, Wang L, Wu Y, Iverson C, Zhou Y, Bowton E, Roden D, Denny J, Aldrich M, Xu H, Zhao Z. Deciphering Signaling Pathway Networks to Understand the Molecular Mechanisms of Metformin Action. PLOS Computational Biology 2015, 11: e1004202. PMID: 26083494, PMCID: PMC4470683, DOI: 10.1371/journal.pcbi.1004202.Peer-Reviewed Original ResearchConceptsGWAS datasetsPathway networkDisease genesGenome-wide association study datasetDrug targetsSignal transduction networksSignal transduction cascadeMultiple signaling pathwaysDrug-induced gene expressionNovel drug targetsTransduction networksTransduction cascadeEnrichment analysisGene expressionCommon genesMolecular mechanismsSignaling pathwaysGenesNovel MycLiterature miningMolecular modePathwayMetformin actionDrug actionDisease pathogenesis
2014
Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality
Xu H, Aldrich M, Chen Q, Liu H, Peterson N, Dai Q, Levy M, Shah A, Han X, Ruan X, Jiang M, Li Y, St Julien J, Warner J, Friedman C, Roden D, Denny J. Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality. Journal Of The American Medical Informatics Association 2014, 22: 179-191. PMID: 25053577, PMCID: PMC4433365, DOI: 10.1136/amiajnl-2014-002649.Peer-Reviewed Original ResearchConceptsType 2 diabetes patientsElectronic health recordsCancer patientsCancer mortalityDiabetes patientsEHR dataNon-diabetic cancer patientsCox proportional hazards modelDrug exposure informationOral hypoglycemic medicationsCharlson Comorbidity IndexNon-diabetic patientsUse of metforminCancer diagnosisHealth recordsSite-specific cancersBody mass indexProportional hazards modelVanderbilt University Medical CenterUniversity Medical CenterLarge electronic health recordHypoglycemic medicationsCause mortalityComorbidity indexInsulin use