{"protocolSection":{"identificationModule":{"nctId":"NCT01107717","orgStudyIdInfo":{"id":"HSC20080456H"},"secondaryIdInfos":[{"id":"5R01DK103841-03","type":"NIH","link":"https://reporter.nih.gov/quickSearch/5R01DK103841-03"}],"organization":{"fullName":"The University of Texas Health Science Center at San Antonio","class":"OTHER"},"briefTitle":"Durability of Combination Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy in New Onset T2DM","officialTitle":"Durability of Early Initial Combination Therapy With Exenatide/Pioglitazone/Metformin vs Conventional Therapy in New Onset Type 2 Diabetes"},"statusModule":{"statusVerifiedDate":"2024-08","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2009-01"},"primaryCompletionDateStruct":{"date":"2023-02-03","type":"ACTUAL"},"completionDateStruct":{"date":"2023-02-03","type":"ACTUAL"},"studyFirstSubmitDate":"2010-04-19","studyFirstSubmitQcDate":"2010-04-20","studyFirstPostDateStruct":{"date":"2010-04-21","type":"ESTIMATED"},"resultsFirstSubmitDate":"2024-03-11","resultsFirstSubmitQcDate":"2024-08-13","resultsFirstPostDateStruct":{"date":"2024-09-05","type":"ACTUAL"},"lastUpdateSubmitDate":"2024-08-13","lastUpdatePostDateStruct":{"date":"2024-09-05","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"The University of Texas Health Science Center at San Antonio","class":"OTHER"},"collaborators":[{"name":"American Diabetes Association","class":"OTHER"},{"name":"Amylin Pharmaceuticals, LLC.","class":"INDUSTRY"},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","class":"NIH"}]},"oversightModule":{"oversightHasDmc":true},"descriptionModule":{"briefSummary":"Type 2 diabetes is a systemic metabolic disease with significant morbidity and mortality due to damaging blood vessels. Increased blood sugar level is a hallmark of diabetes and is an contributes to the development of many of its complications. Multiple defects, e.g. impaired insulin secretion and impaired insulin action, contribute to the development of the disease. The aim of this study is to test the efficacy and durability of combination of drugs which correct the defects that lead to the development of diabetes on achieving adequate and durable control of blood sugar levels. Achieving adequate and durable control of blood sugar will prevent many of diabetes complications.","detailedDescription":"Subjects will be randomized (using a table of random numbers) to receive, in open label fashion, one of the following treatment regimens: (i) Group I will be started on pioglitazone (15 mg/day) plus metformin (1000 mg/day) with the supper meal and exenatide (5 mcg s.c. bid 30 min before breakfast and supper) and up-titrated to 45 pioglitazone plus 2000 metformin and 10 mcg s.c. bid exenatide to achieve HbA1c \\<6.0%; (II) Group II will be started on metformin, 1000 mg with breakfast and 1000 mg with supper, glyburide and basal insulin will be added and up titrated to achieve HbA1c \\<6.0% The study team will compare the efficacy of two therapeutic regimens: (i) triple therapy (pioglitazone, metformin, exenatide) at the time of diagnosis of T2DM versus (ii) stepwise therapy starting with metformin and subsequent addition of sulfonylurea and basal insulin (i.e., the \"standard\" approach) in achieving this goal. The first intervention is based on the novel concept of initiating therapy at the time of diagnosis with combination therapy using agents that correct specific pathophysiologic defects that are characteristic of T2DM (insulin resistance and beta cell failure). The second intervention is based upon stepwise addition of antidiabetic agents to reduce the HbA1C according to the current ADA therapeutic recommendation."},"conditionsModule":{"conditions":["Diabetes"],"keywords":["type 2 diabetes","new onset","combination therapy","new onset type 2 diabetes"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"NONE"}},"enrollmentInfo":{"count":318,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Triple Therapy","type":"EXPERIMENTAL","description":"initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed","interventionNames":["Drug: metformin\\pioglitazone\\exenatide"]},{"label":"conventional therapy","type":"ACTIVE_COMPARATOR","description":"sequential addition of metformin, glyburide and basal insulin","interventionNames":["Drug: metformin, glyburide and glargine"]}],"interventions":[{"type":"DRUG","name":"metformin\\pioglitazone\\exenatide","description":"metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \\< 6.5%","armGroupLabels":["Triple Therapy"]},{"type":"DRUG","name":"metformin, glyburide and glargine","description":"subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \\< 6.5%","armGroupLabels":["conventional therapy"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"HbA1c Level","description":"subjects will be followed for 3 years and the HbA1c measured at this time to provide the values for each arm as defined for the primary outcome of the study","timeFrame":"at the end of the study (3 years)"}],"secondaryOutcomes":[{"measure":"Treatment Failure","description":"Number of participants with HbA1c\\>6.5% at 3 years","timeFrame":"3 years"},{"measure":"Percentage of Patients With Reported Hypoglycemic Events","description":"asymptomatic hypoglycemic events with documented PGC \\< 60 mg/dl and sympotomatic hypoglycemia","timeFrame":"during the entire study (3 years)"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* subjects with type 2 diabetes diagnosed during the past 2 years,\n* above 18 years of age,\n* drug naive, or have been on metformin less than 3 months\n\nExclusion Criteria:\n\n* subjects with type 1 diabetes or GAD positive subjects or subjects with long standing diabetes (\\>2 years) or subjects who are not drug naive or have been on metformin more than 3 months.","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","maximumAge":"80 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Ralph DeFronzo, MD","affiliation":"The University of Texas Health Science Center at San Antonio","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Texas Diabetes Institute","city":"San Antonio","state":"Texas","zip":"78229-3900","country":"United States","geoPoint":{"lat":29.42412,"lon":-98.49363}}]},"referencesModule":{"references":[{"pmid":"33273042","type":"RESULT","citation":"Abdul-Ghani M, Puckett C, Adams J, Khattab A, Baskoy G, Cersosimo E, Triplitt C, DeFronzo RA. Durability of Triple Combination Therapy Versus Stepwise Addition Therapy in Patients With New-Onset T2DM: 3-Year Follow-up of EDICT. Diabetes Care. 2021 Feb;44(2):433-439. doi: 10.2337/dc20-0978. Epub 2020 Dec 3."},{"pmid":"40288809","type":"DERIVED","citation":"Abdul-Ghani M, Puckett C, Abdelgani S, Merovci A, Lavrynenko O, Adams J, Triplitt C, DeFronzo RA. Glycemic and non-glycemic benefits of initial triple therapy versus sequential add-on therapy in patients with new-onset diabetes: results from the EDICT study. BMJ Open Diabetes Res Care. 2025 Apr 27;13(2):e004981. doi: 10.1136/bmjdrc-2025-004981."}]},"ipdSharingStatementModule":{"ipdSharing":"YES","description":"Deidentified data will be shared with local investigators","infoTypes":["STUDY_PROTOCOL","SAP"],"timeFrame":"At study completion after publication in a peer review journal"}},"resultsSection":{"participantFlowModule":{"recruitmentDetails":"Newly diagnosed T2DM participants","groups":[{"id":"FG000","title":"Triple Therapy","description":"initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed\n\nmetformin\\\\pioglitazone\\\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \\< 6.5%"},{"id":"FG001","title":"Conventional Therapy","description":"sequential addition of metformin, glyburide and basal insulin\n\nmetformin, glyburide and glargine: subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \\< 6.5%"}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"157"},{"groupId":"FG001","numSubjects":"161"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"103"},{"groupId":"FG001","numSubjects":"114"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"54"},{"groupId":"FG001","numSubjects":"47"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Triple Therapy","description":"initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed\n\nmetformin\\\\pioglitazone\\\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \\< 6.5%"},{"id":"BG001","title":"Conventional Therapy","description":"sequential addition of metformin, glyburide and basal insulin\n\nmetformin, glyburide and glargine: subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \\< 6.5%"},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"103"},{"groupId":"BG001","value":"114"},{"groupId":"BG002","value":"217"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"44","spread":"1"},{"groupId":"BG001","value":"47","spread":"1"},{"groupId":"BG002","value":"45.5","spread":"1"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"52"},{"groupId":"BG001","value":"72"},{"groupId":"BG002","value":"124"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"51"},{"groupId":"BG001","value":"42"},{"groupId":"BG002","value":"93"}]}]}]},{"title":"Race/Ethnicity, Customized","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"Mexican Americans","categories":[{"measurements":[{"groupId":"BG000","value":"73"},{"groupId":"BG001","value":"75"},{"groupId":"BG002","value":"148"}]}]},{"title":"Caucasian","categories":[{"measurements":[{"groupId":"BG000","value":"15"},{"groupId":"BG001","value":"15"},{"groupId":"BG002","value":"30"}]}]},{"title":"Other","categories":[{"measurements":[{"groupId":"BG000","value":"15"},{"groupId":"BG001","value":"24"},{"groupId":"BG002","value":"39"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"103"},{"groupId":"BG001","value":"114"},{"groupId":"BG002","value":"217"}]}]}]},{"title":"Fasting Plasma Glucose","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"mg/dl","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"203","spread":"6"},{"groupId":"BG001","value":"200","spread":"6"},{"groupId":"BG002","value":"201.5","spread":"6"}]}]}]},{"title":"Diabetes Duration at start","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"Months","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"4.8","spread":"0.5"},{"groupId":"BG001","value":"5.2","spread":"0.5"},{"groupId":"BG002","value":"5","spread":"0.5"}]}]}]},{"title":"Body Mass Index (BMI)","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"kg/m^2","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"36.4","spread":"1.1"},{"groupId":"BG001","value":"36.1","spread":"1.1"},{"groupId":"BG002","value":"36.25","spread":"1.1"}]}]}]},{"title":"Baseline HbA1c","description":"percentage of Hba1c.","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"percentage of glycated hemoglobin","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"9.0","spread":"0.2"},{"groupId":"BG001","value":"8.8","spread":"0.2"},{"groupId":"BG002","value":"8.9","spread":"0.2"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"HbA1c Level","description":"subjects will be followed for 3 years and the HbA1c measured at this time to provide the values for each arm as defined for the primary outcome of the study","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"percentage of glycated hemoglobin","timeFrame":"at the end of the study (3 years)","groups":[{"id":"OG000","title":"Triple Therapy","description":"initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed\n\nmetformin\\\\pioglitazone\\\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \\< 6.5%"},{"id":"OG001","title":"Conventional Therapy","description":"sequential addition of metformin, glyburide and basal insulin\n\nmetformin, glyburide and glargine: subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \\< 6.5%"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"103"},{"groupId":"OG001","value":"114"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"6.9","spread":"0.1"},{"groupId":"OG001","value":"6.4","spread":"0.1"}]}]}]},{"type":"SECONDARY","title":"Treatment Failure","description":"Number of participants with HbA1c\\>6.5% at 3 years","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"number of participants","timeFrame":"3 years","groups":[{"id":"OG000","title":"Triple Therapy","description":"initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed\n\nmetformin\\\\pioglitazone\\\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \\< 6.5%"},{"id":"OG001","title":"Conventional Therapy","description":"sequential addition of metformin, glyburide and basal 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(1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed\n\nmetformin\\\\pioglitazone\\\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \\< 6.5%","deathsNumAffected":0,"deathsNumAtRisk":103,"seriousNumAffected":0,"seriousNumAtRisk":103,"otherNumAffected":44,"otherNumAtRisk":103},{"id":"EG001","title":"Conventional Therapy","description":"sequential addition of metformin, glyburide and basal insulin\n\nmetformin, glyburide and glargine: subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \\< 6.5%","deathsNumAffected":2,"deathsNumAtRisk":114,"seriousNumAffected":0,"seriousNumAtRisk":114,"otherNumAffected":53,"otherNumAtRisk":114}],"otherEvents":[{"term":"Hypoglycemia","organSystem":"Metabolism and nutrition disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":14,"numAffected":14,"numAtRisk":103},{"groupId":"EG001","numEvents":52,"numAffected":52,"numAtRisk":114}]},{"term":"Nausea","organSystem":"Gastrointestinal disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":27,"numAffected":26,"numAtRisk":103},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":114}]},{"term":"Peripheral Edema","organSystem":"Blood and lymphatic system disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":5,"numAffected":5,"numAtRisk":103},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":114}]}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":true},"pointOfContact":{"title":"Muhammad Abdul-Ghani, MD","organization":"University of Texas Health Science Center at San Antonio","email":"abdulghani@uthscsa.edu","phone":"210-557-1157"}}},"documentSection":{"largeDocumentModule":{"largeDocs":[{"typeAbbrev":"Prot_SAP","hasProtocol":true,"hasSap":true,"hasIcf":false,"label":"Study Protocol and Statistical Analysis Plan","date":"2019-12-04","uploadDate":"2024-08-13T10:50","filename":"Prot_SAP_000.pdf","size":621678}]}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-09"},"conditionBrowseModule":{"meshes":[{"id":"D003920","term":"Diabetes Mellitus"},{"id":"D003924","term":"Diabetes Mellitus, Type 2"}],"ancestors":[{"id":"D044882","term":"Glucose Metabolism Disorders"},{"id":"D008659","term":"Metabolic Diseases"},{"id":"D009750","term":"Nutritional and Metabolic Diseases"},{"id":"D004700","term":"Endocrine System Diseases"}]},"interventionBrowseModule":{"meshes":[{"id":"D008687","term":"Metformin"},{"id":"D005905","term":"Glyburide"},{"id":"D000069036","term":"Insulin 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