{"protocolSection":{"identificationModule":{"nctId":"NCT01784965","orgStudyIdInfo":{"id":"17394"},"organization":{"fullName":"Stanford University","class":"OTHER"},"briefTitle":"Liraglutide and a Calorie Restricted Diet Augments Weight Loss and Decreases Risk of Type 2 Diabetes and CVD.","officialTitle":"Addition of a Glucagon-like Peptide-1 to a Calorie Restricted Diet Augments Weight Loss and Decreases Risk of Type 2 Diabetes and Cardiovascular Disease."},"statusModule":{"statusVerifiedDate":"2017-03","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2009-12"},"primaryCompletionDateStruct":{"date":"2012-12","type":"ACTUAL"},"completionDateStruct":{"date":"2012-12","type":"ACTUAL"},"studyFirstSubmitDate":"2013-02-04","studyFirstSubmitQcDate":"2013-02-04","studyFirstPostDateStruct":{"date":"2013-02-06","type":"ESTIMATED"},"resultsFirstSubmitDate":"2016-03-14","resultsFirstSubmitQcDate":"2017-03-15","resultsFirstPostDateStruct":{"date":"2017-04-21","type":"ACTUAL"},"lastUpdateSubmitDate":"2017-03-15","lastUpdatePostDateStruct":{"date":"2017-04-21","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Gerald M Reaven","investigatorTitle":"Professor Emeritus","investigatorAffiliation":"Stanford University"},"leadSponsor":{"name":"Stanford University","class":"OTHER"}},"oversightModule":{"oversightHasDmc":false},"descriptionModule":{"briefSummary":"The goal of this study is to evaluate the hypothesis that the addition of liraglutide, a long-acting glucagon-like peptide 1 (GLP-1) analogue, to a calorie-restricted diet will lead to greater weight loss than will a calorie-restricted diet alone in subjects who are older (50 to 60 years of age), overweight/obese, and prediabetic. These individuals have been selected for study because they are at greatly increased risk to develop type 2 diabetes (2DM) and cardiovascular disease (CVD), and it is hypothesized that the addition of liraglutide to a calorie-restricted diet will significantly decrease risk of these adverse outcomes.\n\nThere is considerable evidence that GLP-I compounds, including liraglutide, improve glycemic control in patients with manifest 2DM. However, there is relatively little information as to the potential utility of these compounds in nondiabetic individual at greatly increased risk of 2DM and CVD. This research proposal is aimed at providing some of this information by quantifying the effects of liraglutide, a long-acting GLP-1 analogue, on weight loss, insulin secretion, insulin action, and multiple CVD risk factors in a very high risk group-older, overweight/obese, prediabetic individuals. Furthermore, by using specific methods, not surrogate estimates, and avoiding the confounding effects of glucotoxicity, it will be possible to gain new insights into the effects of GLP-1 on insulin secretion and insulin action."},"conditionsModule":{"conditions":["Pre-diabetes","Older Adults"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE3"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"PREVENTION","maskingInfo":{"masking":"TRIPLE","whoMasked":["PARTICIPANT","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":69,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"placebo","type":"PLACEBO_COMPARATOR","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo","interventionNames":["Drug: Placebo"]},{"label":"liraglutide","type":"ACTIVE_COMPARATOR","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo","interventionNames":["Drug: liraglutide"]}],"interventions":[{"type":"DRUG","name":"liraglutide","description":"Dosing begins at 0.6 mg subcutaneous injection and increases each week, to 1.2 mg and maximum dose of 1.8 mg.","armGroupLabels":["liraglutide"],"otherNames":["Victoza"]},{"type":"DRUG","name":"Placebo","description":"Double blinded will receive study pen with same dosing instructions starting at 0.6 mg, and each week increase to 1.2 mg and finally 1.8 mg at week three.","armGroupLabels":["placebo"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Change in Weight Reported at 14 Weeks","description":"Change in weight with caloric restriction plus liraglutide vs. caloric restriction and placebo over 14 weeks.","timeFrame":"Baseline and 14 weeks"}],"secondaryOutcomes":[{"measure":"Glucose-stimulated Insulin Secretion in Insulin AUC, Pmol/1x 4H","description":"Absolute change in glucose-stimulated insulin secretion (GS-IS) associated with caloric restriction plus liraglutide vs. caloric restriction and placebo at 14 weeks","timeFrame":"Baseline, 14 weeks"},{"measure":"Insulin Resistance in the Liraglutide vs.Placebo Group After Calorie Restriction","description":"Mean (+/- SD) change in insulin resistance associated with caloric restriction plus liraglutide vs. caloric restriction and placebo.","timeFrame":"Baseline, 14 weeks"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\nIFG, or IGT BMI 27.0-37.0 kg/m2\n\nExclusion Criteria:\n\nDM, CAD, severe anemia, kidney or liver disease, hx of pancreatitis, gallstones, ETOH abuse, personnel or family history of medullary thyroid carcinoma or MEN-2","healthyVolunteers":true,"sex":"ALL","minimumAge":"40 Years","maximumAge":"70 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Gerald M Reaven, M.D.","affiliation":"Stanford University","role":"PRINCIPAL_INVESTIGATOR"}]},"referencesModule":{"references":[{"pmid":"24326527","type":"DERIVED","citation":"Kim SH, Liu A, Ariel D, Abbasi F, Lamendola C, Grove K, Tomasso V, Reaven G. Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised, placebo-controlled study. Diabetologia. 2014 Mar;57(3):455-62. doi: 10.1007/s00125-013-3134-3. Epub 2013 Dec 11."},{"pmid":"23835684","type":"DERIVED","citation":"Kim SH, Abbasi F, Lamendola C, Liu A, Ariel D, Schaaf P, Grove K, Tomasso V, Ochoa H, Liu YV, Chen YD, Reaven G. Benefits of liraglutide treatment in overweight and obese older individuals with prediabetes. Diabetes Care. 2013 Oct;36(10):3276-82. doi: 10.2337/dc13-0354. Epub 2013 Jul 8."}]},"ipdSharingStatementModule":{"ipdSharing":"NO"}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"1 person qualified and enrolled in study but dropped out before being randomized to either group. Therefore is not counted in placebo or liraglutide group.","groups":[{"id":"FG000","title":"Placebo","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo\n\nPlacebo: Double blinded study. Participants will receive study pen with dosing instructions starting at 0.6 mg, and each week increase to 1.2 mg and finally 1.8 mg at week three."},{"id":"FG001","title":"Liraglutide","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo\n\nLiraglutide: Double Blinded study. Participants will receive a study pen with dosing instructions: Dosing begins at 0.6 mg subcutaneous injection and increases each week, to 1.2 mg and maximum dose of 1.8 mg."}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"33"},{"groupId":"FG001","numSubjects":"35"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"27"},{"groupId":"FG001","numSubjects":"24"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"6"},{"groupId":"FG001","numSubjects":"11"}]}],"dropWithdraws":[{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"6"},{"groupId":"FG001","numSubjects":"3"}]},{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"8"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Placebo","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo\n\nPlacebo: Double blinded will receive study pen with same dosing instructions starting at 0.6 mg, and each week increase to 1.2 mg and finally 1.8 mg at week three."},{"id":"BG001","title":"Liraglutide","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo\n\nliraglutide: Dosing begins at 0.6 mg subcutaneous injection and increases each week, to 1.2 mg and maximum dose of 1.8 mg."},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"27"},{"groupId":"BG001","value":"24"},{"groupId":"BG002","value":"51"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"58","spread":"8"},{"groupId":"BG001","value":"58","spread":"7"},{"groupId":"BG002","value":"58","spread":"7.5"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"17"},{"groupId":"BG001","value":"16"},{"groupId":"BG002","value":"33"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"10"},{"groupId":"BG001","value":"8"},{"groupId":"BG002","value":"18"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"27"},{"groupId":"BG001","value":"24"},{"groupId":"BG002","value":"51"}]}]}]},{"title":"BMI","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"kg/m^2","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"31.9","spread":"3.5"},{"groupId":"BG001","value":"31.9","spread":"2.7"},{"groupId":"BG002","value":"31.9","spread":"3.1"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Change in Weight Reported at 14 Weeks","description":"Change in weight with caloric restriction plus liraglutide vs. caloric restriction and placebo over 14 weeks.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"95% Confidence Interval","unitOfMeasure":"kg","timeFrame":"Baseline and 14 weeks","groups":[{"id":"OG000","title":"Placebo","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo\n\nPlacebo: Double blinded will receive study pen with same dosing instructions starting at 0.6 mg, and each week increase to 1.2 mg and finally 1.8 mg at week three."},{"id":"OG001","title":"Liraglutide","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo\n\nliraglutide: Dosing begins at 0.6 mg subcutaneous injection and increases each week, to 1.2 mg and maximum dose of 1.8 mg."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"24"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-3.3","lowerLimit":"-4.1","upperLimit":"-2.5"},{"groupId":"OG001","value":"-6.8","lowerLimit":"-7.8","upperLimit":"-5.9"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"<0.05","statisticalMethod":"t-test, 2 sided"}]},{"type":"SECONDARY","title":"Glucose-stimulated Insulin Secretion in Insulin AUC, Pmol/1x 4H","description":"Absolute change in glucose-stimulated insulin secretion (GS-IS) associated with caloric restriction plus liraglutide vs. caloric restriction and placebo at 14 weeks","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"95% Confidence Interval","unitOfMeasure":"pmol/l x4 h","timeFrame":"Baseline, 14 weeks","groups":[{"id":"OG000","title":"Placebo","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo\n\nPlacebo: Double blinded study. Participants will receive study pen with dosing instructions starting at 0.6 mg, and each week increase to 1.2 mg and finally 1.8 mg at week three."},{"id":"OG001","title":"Liraglutide","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo\n\nLiraglutide: Double Blinded study. Participants will receive a study pen with dosing instructions: Dosing begins at 0.6 mg subcutaneous injection and increases each week, to 1.2 mg and maximum dose of 1.8 mg."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"24"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-7.3","lowerLimit":"-17","upperLimit":"2"},{"groupId":"OG001","value":"34","lowerLimit":"21","upperLimit":"48"}]}]}]},{"type":"SECONDARY","title":"Insulin Resistance in the Liraglutide vs.Placebo Group After Calorie Restriction","description":"Mean (+/- SD) change in insulin resistance associated with caloric restriction plus liraglutide vs. caloric restriction and placebo.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"mg/dL","timeFrame":"Baseline, 14 weeks","groups":[{"id":"OG000","title":"Placebo","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo\n\nPlacebo: Double blinded study. Participants will receive study pen with dosing instructions starting at 0.6 mg, and each week increase to 1.2 mg and finally 1.8 mg at week three."},{"id":"OG001","title":"Liraglutide","description":"Both groups receive dietary weight loss intervention In addition one group received liraglutide and one group received placebo\n\nLiraglutide: Double Blinded study. Participants will receive a study pen with dosing instructions: Dosing begins at 0.6 mg subcutaneous injection and increases each week, to 1.2 mg and maximum dose of 1.8 mg."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"24"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"2.8","spread":"35.9"},{"groupId":"OG001","value":"-57.5","spread":"44.2"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"0","eventGroups":[{"id":"EG000","title":"Liraglutide","description":"Intolerable gastrointestinal side effects 3/35 injection site reaction 2/35 pneumonia 1/35 gallstone 1/35 fall 1/35","seriousNumAffected":8,"seriousNumAtRisk":35,"otherNumAffected":3,"otherNumAtRisk":35},{"id":"EG001","title":"Placebo","description":"0/33 0/33 0/33 0/33 0/33","seriousNumAffected":0,"seriousNumAtRisk":33,"otherNumAffected":6,"otherNumAtRisk":33}],"seriousEvents":[{"term":"Intolerable gastrointestional side effects","organSystem":"Gastrointestinal disorders","stats":[{"groupId":"EG000","numEvents":3,"numAffected":3,"numAtRisk":35},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":33}]},{"term":"injection site reaction","organSystem":"Skin and subcutaneous tissue disorders","stats":[{"groupId":"EG000","numEvents":2,"numAffected":2,"numAtRisk":35},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":33}]},{"term":"pneumonia","organSystem":"Respiratory, thoracic and mediastinal disorders","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":35},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":33}]},{"term":"Gallstones","organSystem":"Gastrointestinal disorders","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":35},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":33}]},{"term":"fall","organSystem":"General disorders","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":35},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":33}]}],"otherEvents":[{"term":"protocol deviation","organSystem":"Investigations","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":35},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":33}]},{"term":"elective back surgery","organSystem":"Surgical and medical procedures","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":35},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":33}]},{"term":"Family issues","organSystem":"Investigations","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":35},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":33}]},{"term":"Decided to withdraw","organSystem":"Investigations","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":35},{"groupId":"EG001","numEvents":6,"numAffected":6,"numAtRisk":33}]}]},"moreInfoModule":{"limitationsAndCaveats":{"description":"Major limitation: the experimental groups were relatively small. In addition, 31% of individuals randomized to liraglutide discontinued participation. Other studies suggest tolerance of GLP-1 receptor agonists may vary by population characteristics."},"certainAgreement":{"piSponsorEmployee":false,"restrictiveAgreement":false},"pointOfContact":{"title":"Gerald Reaven, Professor Emeritus","organization":"Stanford Universtiy","email":"greaven@stanford.edu","phone":"650-724-3416"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-09"},"conditionBrowseModule":{"meshes":[{"id":"D018149","term":"Glucose Intolerance"}],"ancestors":[{"id":"D006943","term":"Hyperglycemia"},{"id":"D044882","term":"Glucose Metabolism Disorders"},{"id":"D008659","term":"Metabolic Diseases"},{"id":"D009750","term":"Nutritional and Metabolic Diseases"}]},"interventionBrowseModule":{"meshes":[{"id":"D000069450","term":"Liraglutide"}],"ancestors":[{"id":"D052216","term":"Glucagon-Like Peptide 1"},{"id":"D004763","term":"Glucagon-Like Peptides"},{"id":"D052336","term":"Proglucagon"},{"id":"D005768","term":"Gastrointestinal Hormones"},{"id":"D006728","term":"Hormones"},{"id":"D006730","term":"Hormones, Hormone Substitutes, and Hormone Antagonists"}]}},"hasResults":true}