2024
Comparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes A Multinational, Federated Analysis of LEGEND-T2DM
Khera R, Aminorroaya A, Dhingra L, Thangaraj P, Pedroso Camargos A, Bu F, Ding X, Nishimura A, Anand T, Arshad F, Blacketer C, Chai Y, Chattopadhyay S, Cook M, Dorr D, Duarte-Salles T, DuVall S, Falconer T, French T, Hanchrow E, Kaur G, Lau W, Li J, Li K, Liu Y, Lu Y, Man K, Matheny M, Mathioudakis N, McLeggon J, McLemore M, Minty E, Morales D, Nagy P, Ostropolets A, Pistillo A, Phan T, Pratt N, Reyes C, Richter L, Ross J, Ruan E, Seager S, Simon K, Viernes B, Yang J, Yin C, You S, Zhou J, Ryan P, Schuemie M, Krumholz H, Hripcsak G, Suchard M. Comparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes A Multinational, Federated Analysis of LEGEND-T2DM. Journal Of The American College Of Cardiology 2024, 84: 904-917. PMID: 39197980, DOI: 10.1016/j.jacc.2024.05.069.Peer-Reviewed Original ResearchConceptsGLP-1 RAsSecond-line agentsGLP-1Antihyperglycemic agentsCardiovascular diseaseMACE riskGlucagon-like peptide-1 receptor agonistsSodium-glucose cotransporter 2 inhibitorsPeptide-1 receptor agonistsDipeptidyl peptidase-4 inhibitorsEffects of SGLT2isType 2 diabetes mellitusPeptidase-4 inhibitorsAdverse cardiovascular eventsCox proportional hazards modelsRandom-effects meta-analysisCardiovascular risk reductionTarget trial emulationProportional hazards model
2022
Revisiting ACCORD: Should Blood Pressure Targets in People With and Without Type 2 Diabetes Be Different?
Du CX, Huang C, Lu Y, Spatz ES, Lipska KJ, Krumholz HM. Revisiting ACCORD: Should Blood Pressure Targets in People With and Without Type 2 Diabetes Be Different? The American Journal Of Medicine 2022, 136: 6-8. PMID: 35981647, DOI: 10.1016/j.amjmed.2022.07.023.Peer-Reviewed Original ResearchLarge-scale evidence generation and evaluation across a network of databases for type 2 diabetes mellitus (LEGEND-T2DM): a protocol for a series of multinational, real-world comparative cardiovascular effectiveness and safety studies
Khera R, Schuemie MJ, Lu Y, Ostropolets A, Chen R, Hripcsak G, Ryan PB, Krumholz HM, Suchard MA. Large-scale evidence generation and evaluation across a network of databases for type 2 diabetes mellitus (LEGEND-T2DM): a protocol for a series of multinational, real-world comparative cardiovascular effectiveness and safety studies. BMJ Open 2022, 12: e057977. PMID: 35680274, PMCID: PMC9185490, DOI: 10.1136/bmjopen-2021-057977.Peer-Reviewed Original ResearchMeSH KeywordsAdultDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsHumansHypoglycemic AgentsReproducibility of ResultsSodium-Glucose Transporter 2 InhibitorsSulfonylurea CompoundsConceptsLarge-scale Evidence GenerationType 2 diabetes mellitusCardiovascular effectivenessDiabetes mellitusSafety outcomesGlucagon-like peptide-1 receptor agonistsSodium-glucose co-transporter-2 inhibitorsMajor adverse cardiovascular eventsNew-user cohort designPeptide-1 receptor agonistsDipeptidyl peptidase-4 inhibitorsSafety studiesAdverse cardiovascular eventsPrimary cardiovascular outcomePeptidase-4 inhibitorsAnti-hyperglycaemic agentsElectronic health record data sourcesEvidence generationCardiovascular eventsCardiovascular outcomesCardiovascular riskActive comparatorTherapeutic optionsReceptor agonistDrug comparisons
2021
Patterns of Prescribing Sodium-Glucose Cotransporter-2 Inhibitors for Medicare Beneficiaries in the United States
Sangha V, Lipska K, Lin Z, Inzucchi SE, McGuire DK, Krumholz HM, Khera R. Patterns of Prescribing Sodium-Glucose Cotransporter-2 Inhibitors for Medicare Beneficiaries in the United States. Circulation Cardiovascular Quality And Outcomes 2021, 14: e008381. PMID: 34779654, PMCID: PMC9022137, DOI: 10.1161/circoutcomes.121.008381.Peer-Reviewed Original ResearchMeSH KeywordsAgedCross-Sectional StudiesDiabetes Mellitus, Type 2GlucoseHumansHypoglycemic AgentsMedicareSodiumSodium-Glucose Transporter 2 InhibitorsUnited StatesConceptsType 2 diabetesMedicare beneficiariesSodium-glucose cotransporter 2 inhibitorsLarge randomized clinical trialsMedicare Part D prescriber dataChronic kidney diseaseCotransporter 2 inhibitorsAtherosclerotic cardiovascular diseasePercent of cliniciansRandomized clinical trialsUS Medicare beneficiariesAdvanced practice providersCross-sectional studyKidney outcomesSGLT2i useSulfonylurea prescriptionUnique cliniciansCardiovascular deathMedication classesKidney diseaseLabel indicationsClinical trialsSGLT2iCardiovascular diseasePractice providersContemporary National Patterns of Eligibility and Utilization of Novel Cardioprotective Anti‐hyperglycemic agents in Type 2 Diabetes
Nargesi AA, Jeyashanmugaraja GP, Desai N, Lipska K, Krumholz H, Khera R. Contemporary National Patterns of Eligibility and Utilization of Novel Cardioprotective Anti‐hyperglycemic agents in Type 2 Diabetes. Journal Of The American Heart Association 2021, 10: e021084. PMID: 33998258, PMCID: PMC8403287, DOI: 10.1161/jaha.121.021084.Peer-Reviewed Original ResearchMeSH KeywordsAgedBiomarkersBlood GlucoseCardiovascular DiseasesDiabetes Mellitus, Type 2Drug UtilizationEligibility DeterminationFemaleGlucagon-Like Peptide-1 ReceptorGuideline AdherenceHeart Disease Risk FactorsHumansIncretinsMaleMiddle AgedNutrition SurveysPractice Guidelines as TopicPractice Patterns, Physicians'Risk AssessmentSodium-Glucose Transporter 2 InhibitorsTime FactorsTreatment OutcomeUnited StatesConceptsSGLT-2 inhibitorsType 2 diabetes mellitusAtherosclerotic cardiovascular diseaseChronic kidney diseaseLarge clinical trialsGLP-1RAsDiabetes mellitusCardiovascular diseaseHeart failureKidney diseaseClinical trialsHigh-risk atherosclerotic cardiovascular diseaseGLP-1RA useAmerican Diabetes AssociationNutrition Examination SurveyAnti-hyperglycemic agentsPublic health benefitsComplex survey designCardiovascular riskGuideline recommendationsDiabetes AssociationExamination SurveyProtective therapyNational HealthAmerican College
2018
Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease
Emdin CA, Khera AV, Chaffin M, Klarin D, Natarajan P, Aragam K, Haas M, Bick A, Zekavat SM, Nomura A, Ardissino D, Wilson JG, Schunkert H, McPherson R, Watkins H, Elosua R, Bown MJ, Samani NJ, Baber U, Erdmann J, Gupta N, Danesh J, Chasman D, Ridker P, Denny J, Bastarache L, Lichtman JH, D’Onofrio G, Mattera J, Spertus JA, Sheu W, Taylor KD, Psaty BM, Rich SS, Post W, Rotter JI, Chen YI, Krumholz H, Saleheen D, Gabriel S, Kathiresan S. Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease. Nature Communications 2018, 9: 1613. PMID: 29691411, PMCID: PMC5915445, DOI: 10.1038/s41467-018-03911-8.Peer-Reviewed Original ResearchMeSH KeywordsDatabases, GeneticDiabetes Mellitus, Type 2DiseaseGene FrequencyGenetic TestingGenetic VariationHumansObesityPhenotypeProteinsRespiratory HypersensitivityUnited KingdomConceptsPLOF variantsProtein-coding genetic variantsFunction variantsCoronary artery diseaseBody fat distributionType 2 diabetesEssential splice siteProtein functionEffector transcriptsUK Biobank participantsIdentifies variantsStop codonMetabolic traitsArtery diseaseSplice siteAllergic diseasesAssociation analysisCardiometabolic diseasesAdditional diseaseFat distributionGenetic variantsBiobank participantsDiseaseBiological effectsVariants
2017
Design and rationale of the Cardiovascular Health and Text Messaging (CHAT) Study and the CHAT-Diabetes Mellitus (CHAT-DM) Study: two randomised controlled trials of text messaging to improve secondary prevention for coronary heart disease and diabetes
Huo X, Spatz ES, Ding Q, Horak P, Zheng X, Masters C, Zhang H, Irwin ML, Yan X, Guan W, Li J, Li X, Spertus JA, Masoudi FA, Krumholz HM, Jiang L. Design and rationale of the Cardiovascular Health and Text Messaging (CHAT) Study and the CHAT-Diabetes Mellitus (CHAT-DM) Study: two randomised controlled trials of text messaging to improve secondary prevention for coronary heart disease and diabetes. BMJ Open 2017, 7: e018302. PMID: 29273661, PMCID: PMC5778311, DOI: 10.1136/bmjopen-2017-018302.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBlood PressureChinaCoronary DiseaseDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2ExerciseFemaleGlycated HemoglobinHumansLife StyleMaleMedication AdherenceMiddle AgedMotivationResearch DesignRisk FactorsSecondary PreventionSelf CareSingle-Blind MethodTelemedicineText MessagingYoung AdultConceptsSystolic blood pressureBody mass indexTrials of textProportion of patientsMedication adherencePhysical activitySecondary outcomesPrimary outcomeSmoking cessationCardiovascular healthMellitus StudySecondary coronary heart disease preventionCoronary heart disease preventionLow-density lipoprotein cholesterolUsual scientific forumsBlood pressure controlRisk factor managementHeart disease preventionCoronary heart diseaseMobile health interventionsInstitutional review boardUniversity Institutional Review BoardBehavioral skills modelText messagingBehavioral change techniquesIs Hemoglobin A1c the Right Outcome for Studies of Diabetes?
Lipska KJ, Krumholz HM. Is Hemoglobin A1c the Right Outcome for Studies of Diabetes? JAMA 2017, 317: 1017-1018. PMID: 28125758, PMCID: PMC5350060, DOI: 10.1001/jama.2017.0029.Commentaries, Editorials and Letters
2016
Trends in Drug Utilization, Glycemic Control, and Rates of Severe Hypoglycemia, 2006–2013
Lipska KJ, Yao X, Herrin J, McCoy RG, Ross JS, Steinman MA, Inzucchi SE, Gill TM, Krumholz HM, Shah ND. Trends in Drug Utilization, Glycemic Control, and Rates of Severe Hypoglycemia, 2006–2013. Diabetes Care 2016, 40: 468-475. PMID: 27659408, PMCID: PMC5360291, DOI: 10.2337/dc16-0985.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedBlood GlucoseComorbidityDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsDrug UtilizationFemaleGlycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsInsulinLogistic ModelsMaleMetforminMiddle AgedRetrospective StudiesSulfonylurea CompoundsThiazolidinedionesYoung AdultConceptsGlycemic controlSevere hypoglycemiaOlder patientsDipeptidyl peptidase-4 inhibitorsGlucose-lowering drugsGlucose-lowering medicationsProportion of patientsOverall glycemic controlPeptidase-4 inhibitorsMedicare Advantage patientsSex-standardized ratesType 2 diabetesOverall rateClass of agentsMore comorbiditiesChronic comorbiditiesYounger patientsAdvantage patientsDrug utilizationClaims dataPatientsHypoglycemiaHemoglobin AT2DMComorbiditiesPolypharmacy in the Aging Patient: A Review of Glycemic Control in Older Adults With Type 2 Diabetes
Lipska KJ, Krumholz H, Soones T, Lee SJ. Polypharmacy in the Aging Patient: A Review of Glycemic Control in Older Adults With Type 2 Diabetes. JAMA 2016, 315: 1034-1045. PMID: 26954412, PMCID: PMC4823136, DOI: 10.1001/jama.2016.0299.BooksConceptsRandomized clinical trialsIntensive glycemic controlGlycemic controlClinical trialsOlder adultsMicrovascular outcomesTreatment burdenPatient preferencesMost RCTsLarge randomized clinical trialsType 2 diabetes mellitusMajor macrovascular eventsStandard glycemic controlOptimal glycemic controlLower treatment burdenSurrogate end pointsHigh-quality evidenceType 2 diabetesLikelihood of benefitMajority of adultsGlycemic treatmentMacrovascular eventsDiabetes mellitusPatient factorsAging Patient
2015
Qingdao Port Cardiovascular Health Study: a prospective cohort study
Spatz ES, Jiang X, Lu J, Masoudi FA, Spertus JA, Wang Y, Li X, Downing NS, Nasir K, Du X, Li J, Krumholz HM, Liu X, Jiang L. Qingdao Port Cardiovascular Health Study: a prospective cohort study. BMJ Open 2015, 5: e008403. PMID: 26656011, PMCID: PMC4679897, DOI: 10.1136/bmjopen-2015-008403.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAsian PeopleBody Mass IndexCardiovascular DiseasesChinaCohort StudiesCost of IllnessDiabetes Mellitus, Type 2Early DiagnosisEnvironmental ExposureFemaleHealth BehaviorHealth SurveysHumansHyperlipidemiasHypertensionIncidenceMaleMiddle AgedOccupational ExposurePhysical ExaminationPreventive Health ServicesProspective StudiesRisk FactorsSelf ReportSocioeconomic FactorsWorkplaceConceptsAnnual health assessmentCardiovascular diseaseRisk factorsUnique risk factor profileCardiovascular risk factorsClinical risk factorsProspective cohort studyRisk factor profileHospital medical recordsCardiovascular Health StudyPopulation-based studyPopulation-based strategiesHealth assessmentCardiovascular outcomesCohort studyCarotid ultrasoundMean agePhysical examinationCardiovascular healthHeart diseaseMedical recordsDisease onsetMedical insurance claimsHealth StudyUrine analysis
2014
Comparing Diabetes Medications: Where Do We Set the Bar?
Lipska KJ, Krumholz HM. Comparing Diabetes Medications: Where Do We Set the Bar? JAMA Internal Medicine 2014, 174: 317-318. PMID: 24366351, PMCID: PMC5459364, DOI: 10.1001/jamainternmed.2013.13433.Commentaries, Editorials and Letters
2013
HbA1c and Risk of Severe Hypoglycemia in Type 2 Diabetes
Lipska KJ, Warton EM, Huang ES, Moffet HH, Inzucchi SE, Krumholz HM, Karter AJ. HbA1c and Risk of Severe Hypoglycemia in Type 2 Diabetes. Diabetes Care 2013, 36: 3535-3542. PMID: 23900589, PMCID: PMC3816866, DOI: 10.2337/dc13-0610.Peer-Reviewed Original ResearchConceptsSevere hypoglycemiaType 2 diabetesRelative riskGlycemic controlSelf-reported severe hypoglycemiaType 2 diabetic patientsGlucose-lowering therapyPoor glycemic controlRate of hypoglycemiaPotential effect modifiersIntegrated healthcare systemYears of ageEligible survey respondentsPoisson regression modelsDiabetes durationDiabetes medicationsDiabetic patientsClinical variablesDiabetes StudyNormal glycemiaMain exposureEffect modifiersHypoglycemiaType 2PatientsPrevalence of Traditional Cardiac Risk Factors and Secondary Prevention Among Patients Hospitalized for Acute Myocardial Infarction (AMI): Variation by Age, Sex, and Race
Leifheit-Limson EC, Spertus JA, Reid KJ, Jones SB, Vaccarino V, Krumholz HM, Lichtman JH. Prevalence of Traditional Cardiac Risk Factors and Secondary Prevention Among Patients Hospitalized for Acute Myocardial Infarction (AMI): Variation by Age, Sex, and Race. Journal Of Women's Health 2013, 22: 659-666. PMID: 23841468, DOI: 10.1089/jwh.2012.3962.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overBlack or African AmericanBody Mass IndexCounselingDiabetes Mellitus, Type 2FemaleHospitalizationHumansHypercholesterolemiaHypertensionLife StyleMaleMiddle AgedMyocardial InfarctionObesityPrevalenceProspective StudiesRisk FactorsSecondary PreventionSex FactorsSmokingSmoking CessationSocioeconomic FactorsWhite PeopleConceptsCardiac risk factorsAcute myocardial infarctionSecondary prevention effortsTraditional cardiac risk factorsLipid-lowering medicationsRisk factorsWhite patientsAMI patientsMyocardial infarctionPrevention effortsGreater risk factor burdenMultiple cardiac risk factorsRisk factor burdenYoung black patientsYoung white patientsSecondary prevention strategiesRisk factor prevalenceHigh-risk subgroupsMultiple risk factorsBlack womenAge-sex groupsOlder patientsSecondary preventionYounger patientsFactor prevalence
2012
Role of Intensive Glucose Control in Development of Renal End Points in Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis
Coca SG, Ismail-Beigi F, Haq N, Krumholz HM, Parikh CR. Role of Intensive Glucose Control in Development of Renal End Points in Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis. JAMA Internal Medicine 2012, 172: 761-769. PMID: 22636820, PMCID: PMC3688081, DOI: 10.1001/archinternmed.2011.2230.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBlood GlucoseDiabetes Mellitus, Type 2Diabetic NephropathiesDisease ProgressionFemaleGlycated HemoglobinHumansHypoglycemic AgentsKidney Failure, ChronicKidney Function TestsMaleMiddle AgedMonitoring, PhysiologicPrognosisRandomized Controlled Trials as TopicRenal DialysisRisk AssessmentSeverity of Illness IndexConceptsIntensive glucose controlRenal end pointsSerum creatinine levelsConventional glucose controlGlucose controlType 2 diabetesRenal diseaseCreatinine levelsEnd pointGlycemic controlSystematic reviewType 2 diabetes mellitusAggressive glycemic controlClinical renal outcomesKidney-related outcomesIntensive glycemic controlRenal outcomesCumulative incidenceDiabetes mellitusRandomized trialsConventional therapyLanguage restrictionsMacroalbuminuriaMicroalbuminuriaType 2
2011
Use of Fibrates in the United States and Canada
Jackevicius CA, Tu JV, Ross JS, Ko DT, Carreon D, Krumholz HM. Use of Fibrates in the United States and Canada. JAMA 2011, 305: 1217-1224. PMID: 21427374, PMCID: PMC3332101, DOI: 10.1001/jama.2011.353.Peer-Reviewed Original ResearchMeSH KeywordsCanadaCardiovascular DiseasesCohort StudiesCosts and Cost AnalysisDiabetes Mellitus, Type 2Drug CostsDrugs, GenericFenofibrateFibric AcidsHealth ExpendituresHumansHydroxymethylglutaryl-CoA Reductase InhibitorsHypolipidemic AgentsMedical AuditPractice Patterns, Physicians'PrescriptionsUnited StatesConceptsUse of fibratesRole of fibratesObservational cohort studyIMS Health dataFenofibrate useCardiovascular riskCohort studyDiabetes (ACCORD) trialClinical benefitFibratesMonthsPrescriptionUnited StatesPatientsNegative resultsFenofibrateHealth dataCurrent useGeneric formulationPopulationStatinsTherapyTrialsUse of GLP-1 analogues needs great caution
Yudkin JS, Lehman R, Krumholz HM. Use of GLP-1 analogues needs great caution. The BMJ 2011, 342: d1478. PMID: 21385813, DOI: 10.1136/bmj.d1478.Peer-Reviewed Original ResearchDiabetes Mellitus, Type 2Diabetic AngiopathiesGlucagon-Like Peptide 1Glycated HemoglobinHumansHypoglycemic Agents
2010
Responding to an FDA Warning — Geographic Variation in the Use of Rosiglitazone
Shah ND, Montori VM, Krumholz HM, Tu K, Alexander GC, Jackevicius CA. Responding to an FDA Warning — Geographic Variation in the Use of Rosiglitazone. New England Journal Of Medicine 2010, 363: 2081-2084. PMID: 21083379, DOI: 10.1056/nejmp1011042.Peer-Reviewed Original ResearchLicensing drugs for diabetes
Lehman R, Yudkin JS, Krumholz H. Licensing drugs for diabetes. The BMJ 2010, 341: c4805. PMID: 20819887, DOI: 10.1136/bmj.c4805.Peer-Reviewed Original ResearchMeSH KeywordsCardiovascular DiseasesDiabetes Mellitus, Type 2Drug ApprovalHumansHypoglycemic AgentsRosiglitazoneSafety-Based Drug WithdrawalsThiazolidinedionesDiscontinuation of Antihyperglycemic Therapy and Clinical Outcomes After Acute Myocardial Infarction in Older Patients With Diabetes
Lipska KJ, Wang Y, Kosiborod M, Masoudi FA, Havranek EP, Krumholz HM, Inzucchi SE. Discontinuation of Antihyperglycemic Therapy and Clinical Outcomes After Acute Myocardial Infarction in Older Patients With Diabetes. Circulation Cardiovascular Quality And Outcomes 2010, 3: 236-242. PMID: 20354220, DOI: 10.1161/circoutcomes.109.887620.Peer-Reviewed Original ResearchConceptsAcute myocardial infarctionAntihyperglycemic therapyAntihyperglycemic agentsOlder patientsMyocardial infarctionMortality rateMultivariable Cox proportional hazards modelsCox proportional hazards modelFrequency of discontinuationGlucose-lowering agentsGlucose-lowering therapyInclusion/exclusion criteriaProportional hazards modelYear of dischargeHigh mortality rateDiabetic regimenFirst rehospitalizationReadmission ratesSecondary outcomesHeart failurePrimary outcomeClinical outcomesMultivariable analysisRetrospective studyIndependent association