Ignite Creation Date:
2025-12-24 @ 4:02 PM
Ignite Modification Date:
2025-12-28 @ 10:48 AM
Study NCT ID:
NCT00855166
Status:
COMPLETED
Last Update Posted:
2013-10-14
First Post:
2009-03-03
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Evaluation of the Effect of Dapagliflozin in Combination With Metformin on Body Weight in Subjects With Type 2 Diabetes
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003924', 'term': 'Diabetes Mellitus, Type 2'}, {'id': 'D001835', 'term': 'Body Weight'}], 'ancestors': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C529054', 'term': 'dapagliflozin'}, {'id': 'D008687', 'term': 'Metformin'}, {'id': 'D000068900', 'term': 'Sitagliptin Phosphate'}], 'ancestors': [{'id': 'D001645', 'term': 'Biguanides'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D014230', 'term': 'Triazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011719', 'term': 'Pyrazines'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'ClinicalTrialTransparency@astrazeneca.com', 'title': 'Eva Johnsson', 'organization': 'AstraZeneca'}, 'certainAgreement': {'otherDetails': 'If an Investigator requests permission to publish data from this study any such publication is to be agreed with AstraZeneca (AZ) in advance. The investigator agrees to provide AZ as soon as possible with drafts of proposed publications. Unless otherwise agreed, AZ shall have a period of 60 days from receipt of the proposed final manuscript to review it and may within such time require that submission for publication of the manuscript be delayed in order for AZ to file patent applications.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}, 'limitationsAndCaveats': {'description': 'For participants who did not complete 24 weeks, last observation carried forward (LOCF) was used.'}}, 'adverseEventsModule': {'timeFrame': 'Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 24-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.', 'description': 'Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo Plus Metformin', 'description': 'Placebo oral once daily plus metformin over 24 weeks', 'otherNumAtRisk': 91, 'otherNumAffected': 9, 'seriousNumAtRisk': 91, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': 'Dapagliflozin Plus Metformin', 'description': 'Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks', 'otherNumAtRisk': 91, 'otherNumAffected': 7, 'seriousNumAtRisk': 91, 'seriousNumAffected': 6}], 'otherEvents': [{'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 91, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 91, 'numAffected': 6}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 91, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 91, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}], 'seriousEvents': [{'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 91, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 91, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Vertigo', 'stats': [{'groupId': 'EG000', 'numAtRisk': 91, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 91, 'numAffected': 1}], 'organSystem': 'Ear and labyrinth disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Oesophageal varices hemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 91, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 91, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Spinal osteoarthritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 91, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 91, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Transient ischemic attack', 'stats': [{'groupId': 'EG000', 'numAtRisk': 91, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 91, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 91, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 91, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Ulcerative keratitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 91, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 91, 'numAffected': 0}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Adjusted Mean Change in Total Body Weight', 'denoms': [{'units': 'Participants', 'counts': [{'value': '91', 'groupId': 'OG000'}, {'value': '89', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Plus Metformin', 'description': 'Placebo oral once daily plus metformin over 24 weeks'}, {'id': 'OG001', 'title': 'Dapagliflozin Plus Metformin', 'description': 'Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.88', 'spread': '0.2746', 'groupId': 'OG000', 'lowerLimit': '-1.43', 'upperLimit': '-0.34'}, {'value': '-2.96', 'spread': '0.2766', 'groupId': 'OG001', 'lowerLimit': '-3.51', 'upperLimit': '-2.41'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-2.08', 'ciLowerLimit': '-2.84', 'ciUpperLimit': '-1.31', 'pValueComment': 'Significant at alpha=0.05 (2-sided)', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.3885', 'groupDescription': 'H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'with treatment group and stratum (gender) as effects and baseline value as covariate', 'testedNonInferiority': False}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 24', 'description': 'To evaluate the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin on total body weight after 24 weeks of oral administration of double-blind treatment.', 'unitOfMeasure': 'kg', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values'}, {'type': 'SECONDARY', 'title': 'Adjusted Mean Change in Waist Circumference', 'denoms': [{'units': 'Participants', 'counts': [{'value': '91', 'groupId': 'OG000'}, {'value': '89', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Plus Metformin', 'description': 'Placebo oral once daily plus metformin over 24 weeks'}, {'id': 'OG001', 'title': 'Dapagliflozin Plus Metformin', 'description': 'Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.99', 'spread': '0.4349', 'groupId': 'OG000', 'lowerLimit': '-1.84', 'upperLimit': '-0.13'}, {'value': '-2.51', 'spread': '0.4388', 'groupId': 'OG001', 'lowerLimit': '-3.38', 'upperLimit': '-1.64'}]}]}], 'analyses': [{'pValue': '0.0143', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-1.52', 'ciLowerLimit': '-2.74', 'ciUpperLimit': '-0.31', 'pValueComment': "Significant at alpha=0.05 (2-sided). Results of key secondary endpoints are interpreted using Hochberg's method", 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.6162', 'groupDescription': 'H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'with treatment group and stratum (gender) as effects and baseline value as covariate', 'testedNonInferiority': False}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 24', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on waist circumference.', 'unitOfMeasure': 'cm', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values'}, {'type': 'SECONDARY', 'title': 'Adjusted Mean Change in Body Fat Mass', 'denoms': [{'units': 'Participants', 'counts': [{'value': '79', 'groupId': 'OG000'}, {'value': '82', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Plus Metformin', 'description': 'Placebo oral once daily plus metformin over 24 weeks'}, {'id': 'OG001', 'title': 'Dapagliflozin Plus Metformin', 'description': 'Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.74', 'spread': '0.2670', 'groupId': 'OG000', 'lowerLimit': '-1.27', 'upperLimit': '-0.22'}, {'value': '-2.22', 'spread': '0.2626', 'groupId': 'OG001', 'lowerLimit': '-2.74', 'upperLimit': '-1.70'}]}]}], 'analyses': [{'pValue': '0.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-1.48', 'ciLowerLimit': '-2.22', 'ciUpperLimit': '-0.74', 'pValueComment': "Significant at alpha=0.05 (2-sided). Results of key secondary endpoints are interpreted using Hochberg's method", 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.3731', 'groupDescription': 'H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'with treatment group and stratum (gender) as effects and baseline value as covariate', 'testedNonInferiority': False}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 24', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on total body fat mass measured by dual energy X-ray absorptiometry.', 'unitOfMeasure': 'kg', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants With Body Weight Decrease ≥5%', 'denoms': [{'units': 'Participants', 'counts': [{'value': '91', 'groupId': 'OG000'}, {'value': '89', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Plus Metformin', 'description': 'Placebo oral once daily plus metformin over 24 weeks'}, {'id': 'OG001', 'title': 'Dapagliflozin Plus Metformin', 'description': 'Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '4.3', 'groupId': 'OG000', 'lowerLimit': '0.1', 'upperLimit': '8.6'}, {'value': '30.6', 'groupId': 'OG001', 'lowerLimit': '21.1', 'upperLimit': '40.2'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Risk Difference (RD)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '26.3', 'ciLowerLimit': '15.9', 'ciUpperLimit': '36.7', 'pValueComment': "Significant at alpha=0.05 (2-sided). Results of key secondary endpoints are interpreted using Hochberg's method", 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '5.309', 'groupDescription': 'H0: proportion(treat) minus proportion(placebo) = 0 versus the alternative HA: proportion(treat) minus proportion(placebo) =/= 0', 'statisticalMethod': 'Regression, Logistic', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Based on methodology of Zhang, Tsiatis \\& Davidian and Davidian, Tsiatis, Zhang \\& Lu, with adjustment for baseline value and stratum (gender).', 'testedNonInferiority': False}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 24', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on body weight decrease ≥5%. Least Squares Mean represents the percent of participants adjusted for body weight baseline value.', 'unitOfMeasure': 'Percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Adjusted Percent Change in Bone Mineral Density (BMD) at Lumbar Spine (L1-4)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '71', 'groupId': 'OG000'}, {'value': '68', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Plus Metformin', 'description': 'Placebo oral once daily plus metformin over 102 weeks'}, {'id': 'OG001', 'title': 'Dapagliflozin Plus Metformin', 'description': 'Dapagliflozin 10 mg oral once daily plus metformin over 102 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '0.47', 'groupId': 'OG000', 'lowerLimit': '-0.32', 'upperLimit': '1.27'}, {'value': '0.69', 'groupId': 'OG001', 'lowerLimit': '-0.19', 'upperLimit': '1.57'}]}]}], 'analyses': [{'pValue': '0.7013', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.22', 'ciLowerLimit': '-0.89', 'ciUpperLimit': '1.34', 'pValueComment': 'Exploratory. Model including fixed categorical effects of treatment, week, treatment-by-week interaction, gender and rescue medication as well as continuous fixed covariates of baseline measurement and baseline measurement-by-week interaction.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.5652', 'estimateComment': 'Natural logarithms of baseline and week 102 values were used.', 'groupDescription': 'H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Percent change in BMD from baseline to week 102 evaluated via longitudinal repeated measures analysis using direct likelihood.', 'testedNonInferiority': False}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 102', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at lumbar spine (L1-4) as measured by Dual Energy X-ray Absorptiometry.', 'unitOfMeasure': 'Percent', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety Analysis Set (all participants who received at least one dose of double-blind study medication)'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Adjusted Percent Change in Bone Mineral Density (BMD) at Femoral Neck', 'denoms': [{'units': 'Participants', 'counts': [{'value': '71', 'groupId': 'OG000'}, {'value': '68', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Plus Metformin', 'description': 'Placebo oral once daily plus metformin over 102 weeks'}, {'id': 'OG001', 'title': 'Dapagliflozin Plus Metformin', 'description': 'Dapagliflozin 10 mg oral once daily plus metformin over 102 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '0.09', 'groupId': 'OG000', 'lowerLimit': '-0.83', 'upperLimit': '1.01'}, {'value': '-0.85', 'groupId': 'OG001', 'lowerLimit': '-1.85', 'upperLimit': '0.16'}]}]}], 'analyses': [{'pValue': '0.1521', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.94', 'ciLowerLimit': '-2.21', 'ciUpperLimit': '0.35', 'pValueComment': 'Exploratory. Model including fixed categorical effects of treatment, week, treatment-by-week interaction, gender and rescue medication as well as continuous fixed covariates of baseline measurement and baseline measurement-by-week interaction.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.6473', 'estimateComment': 'Natural logarithms of baseline and week 102 values were used.', 'groupDescription': 'H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Percent change in BMD from baseline to week 102 evaluated via longitudinal repeated measures analysis using direct likelihood.', 'testedNonInferiority': False}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 102', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at femoral neck as measured by Dual Energy X-ray Absorptiometry.', 'unitOfMeasure': 'Percent', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety Analysis Set (all participants who received at least one dose of double-blind study medication)'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Adjusted Percent Change in Bone Mineral Density (BMD) at Total Hip', 'denoms': [{'units': 'Participants', 'counts': [{'value': '71', 'groupId': 'OG000'}, {'value': '68', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo Plus Metformin', 'description': 'Placebo oral once daily plus metformin over 102 weeks'}, {'id': 'OG001', 'title': 'Dapagliflozin Plus Metformin', 'description': 'Dapagliflozin 10 mg oral once daily plus metformin over 102 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.37', 'groupId': 'OG000', 'lowerLimit': '-1.00', 'upperLimit': '0.26'}, {'value': '-0.82', 'groupId': 'OG001', 'lowerLimit': '-1.52', 'upperLimit': '-0.12'}]}]}], 'analyses': [{'pValue': '0.3105', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.45', 'ciLowerLimit': '-1.32', 'ciUpperLimit': '0.43', 'pValueComment': 'Exploratory. Model including fixed categorical effects of treatment, week, treatment-by-week interaction, gender and rescue medication as well as continuous fixed covariates of baseline measurement and baseline measurement-by-week interaction.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.4428', 'estimateComment': 'Natural logarithms of baseline and week 102 values were used.', 'groupDescription': 'H0: mean(treat) minus mean(placebo) = 0 versus the alternative HA: mean(treat) minus mean(placebo) =/= 0', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Percent change in BMD from baseline to week 102 evaluated via longitudinal repeated measures analysis using direct likelihood.', 'testedNonInferiority': False}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 102', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at total hip as measured by Dual Energy X-ray Absorptiometry.', 'unitOfMeasure': 'Percent', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety Analysis Set (all participants who received at least one dose of double-blind study medication)'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Placebo Plus Metformin', 'description': 'Placebo oral once daily plus metformin over 24 weeks'}, {'id': 'FG001', 'title': 'Dapagliflozin Plus Metformin', 'description': 'Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '91'}, {'comment': 'Of the 91 randomized participants only 89 were included in the full analysis set.', 'groupId': 'FG001', 'numSubjects': '91'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '86'}, {'groupId': 'FG001', 'numSubjects': '83'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '8'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '2'}]}, {'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '4'}]}, {'type': 'Poor/non-compliance', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Administrative reasons by sponsor', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Subject no longer meets study criteria', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'First participant enrolled: 13 Feb 2009. Last participant completed 24 week period: 03 Jun 2010. 314 participants were enrolled, 182 were randomized in 40 centers in 5 European countries. Men aged 30-75 years and women aged 55-75 years with inadequate glycemic control (HbA1c 6.5% to 8.5%), BMI of at least 25 kg/sqm and body weight \\<= 120 kg.', 'preAssignmentDetails': 'During a placebo lead-in period, participants were counselled on dietary and life-style modifications. The metformin dose was adjusted to open label 1500 mg/day, 2000 mg/day or 2500 mg/day. Neither gender should exceed 60% of the total number of randomized participants.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '91', 'groupId': 'BG000'}, {'value': '89', 'groupId': 'BG001'}, {'value': '180', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Placebo Plus Metformin', 'description': 'Placebo oral once daily plus metformin over 24 weeks'}, {'id': 'BG001', 'title': 'Dapagliflozin Plus Metformin', 'description': 'Dapagliflozin 10 mg oral once daily plus metformin over 24 weeks'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age Continuous', 'classes': [{'categories': [{'measurements': [{'value': '60.8', 'spread': '6.82', 'groupId': 'BG000'}, {'value': '60.6', 'spread': '8.16', 'groupId': 'BG001'}, {'value': '60.7', 'spread': '7.49', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '40', 'groupId': 'BG000'}, {'value': '40', 'groupId': 'BG001'}, {'value': '80', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '51', 'groupId': 'BG000'}, {'value': '49', 'groupId': 'BG001'}, {'value': '100', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'White', 'categories': [{'measurements': [{'value': '91', 'groupId': 'BG000'}, {'value': '89', 'groupId': 'BG001'}, {'value': '180', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'Participants'}, {'title': 'Body Weight', 'classes': [{'categories': [{'measurements': [{'value': '90.91', 'spread': '13.716', 'groupId': 'BG000'}, {'value': '92.06', 'spread': '14.128', 'groupId': 'BG001'}, {'value': '91.48', 'spread': '13.894', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Kilogram', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Body Mass Index', 'classes': [{'categories': [{'measurements': [{'value': '31.68', 'spread': '3.890', 'groupId': 'BG000'}, {'value': '32.06', 'spread': '3.887', 'groupId': 'BG001'}, {'value': '31.87', 'spread': '3.882', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg/m2', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Glycosylated hemoglobin A1c (HbA1c)', 'classes': [{'categories': [{'measurements': [{'value': '7.16', 'spread': '0.531', 'groupId': 'BG000'}, {'value': '7.19', 'spread': '0.443', 'groupId': 'BG001'}, {'value': '7.17', 'spread': '0.489', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Percent', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Fasting Plasma Glucose', 'classes': [{'categories': [{'measurements': [{'value': '149.60', 'spread': '25.086', 'groupId': 'BG000'}, {'value': '148.01', 'spread': '24.650', 'groupId': 'BG001'}, {'value': '148.82', 'spread': '24.815', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Milligram per deciliter', 'dispersionType': 'STANDARD_DEVIATION'}], 'populationDescription': 'Full Analysis Set defined as all randomized participants (as randomized) who received at least one dose of double-blind study medication, who have a non-missing baseline value and at least one post-baseline efficacy value for at least one efficacy variable during double-blind treatment period.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 182}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-02'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-08', 'completionDateStruct': {'date': '2011-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2013-08-09', 'studyFirstSubmitDate': '2009-03-03', 'resultsFirstSubmitDate': '2013-01-21', 'studyFirstSubmitQcDate': '2009-03-03', 'lastUpdatePostDateStruct': {'date': '2013-10-14', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2013-08-09', 'studyFirstPostDateStruct': {'date': '2009-03-04', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2013-10-14', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2010-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Adjusted Percent Change in Bone Mineral Density (BMD) at Lumbar Spine (L1-4)', 'timeFrame': 'Baseline to Week 102', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at lumbar spine (L1-4) as measured by Dual Energy X-ray Absorptiometry.'}, {'measure': 'Adjusted Percent Change in Bone Mineral Density (BMD) at Femoral Neck', 'timeFrame': 'Baseline to Week 102', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at femoral neck as measured by Dual Energy X-ray Absorptiometry.'}, {'measure': 'Adjusted Percent Change in Bone Mineral Density (BMD) at Total Hip', 'timeFrame': 'Baseline to Week 102', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at total hip as measured by Dual Energy X-ray Absorptiometry.'}], 'primaryOutcomes': [{'measure': 'Adjusted Mean Change in Total Body Weight', 'timeFrame': 'Baseline to Week 24', 'description': 'To evaluate the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin on total body weight after 24 weeks of oral administration of double-blind treatment.'}], 'secondaryOutcomes': [{'measure': 'Adjusted Mean Change in Waist Circumference', 'timeFrame': 'Baseline to Week 24', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on waist circumference.'}, {'measure': 'Adjusted Mean Change in Body Fat Mass', 'timeFrame': 'Baseline to Week 24', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on total body fat mass measured by dual energy X-ray absorptiometry.'}, {'measure': 'Proportion of Participants With Body Weight Decrease ≥5%', 'timeFrame': 'Baseline to Week 24', 'description': 'To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on body weight decrease ≥5%. Least Squares Mean represents the percent of participants adjusted for body weight baseline value.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Dapagliflozin', 'Metformin', 'Type 2 diabetes', 'body weight'], 'conditions': ['Type 2 Diabetes Mellitus']}, 'referencesModule': {'references': [{'pmid': '38770818', 'type': 'DERIVED', 'citation': 'Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.'}, {'pmid': '26894924', 'type': 'DERIVED', 'citation': 'Kohan DE, Fioretto P, Johnsson K, Parikh S, Ptaszynska A, Ying L. The effect of dapagliflozin on renal function in patients with type 2 diabetes. J Nephrol. 2016 Jun;29(3):391-400. doi: 10.1007/s40620-016-0261-1. Epub 2016 Feb 19.'}, {'pmid': '23906445', 'type': 'DERIVED', 'citation': 'Bolinder J, Ljunggren O, Johansson L, Wilding J, Langkilde AM, Sjostrom CD, Sugg J, Parikh S. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014 Feb;16(2):159-69. doi: 10.1111/dom.12189. Epub 2013 Aug 29.'}, {'pmid': '22651373', 'type': 'DERIVED', 'citation': 'Ljunggren O, Bolinder J, Johansson L, Wilding J, Langkilde AM, Sjostrom CD, Sugg J, Parikh S. Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin. Diabetes Obes Metab. 2012 Nov;14(11):990-9. doi: 10.1111/j.1463-1326.2012.01630.x. Epub 2012 Jun 29.'}]}, 'descriptionModule': {'briefSummary': 'This study is being carried out to see if dapagliflozin in addition to metformin decreases body weight and if so, how it compares with metformin alone.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '30 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Type 2 diabetes\n* Ongoing treatment with metformin on a stable dose of ≥1500 mg/day for at least 12 weeks prior to enrolment\n* Inadequate glycemic control, defined as HbA1c ≥6.5% and ≤8.5%\n* ≥30 years for males\n* ≥55 years for females\n\nExclusion Criteria:\n\n* Type 1 Diabetes\n* Body weight change \\>5% within 3 months prior to enrolment\n* Renal and liver impairment'}, 'identificationModule': {'nctId': 'NCT00855166', 'briefTitle': 'Evaluation of the Effect of Dapagliflozin in Combination With Metformin on Body Weight in Subjects With Type 2 Diabetes', 'organization': {'class': 'INDUSTRY', 'fullName': 'AstraZeneca'}, 'officialTitle': 'A 24-week,Multi-centre,Int.,Double-blind,Rand.,Parallel-group,Plac.-Controlled,Phase III Study With a 78-week Ext.Per. to Evaluate the Effect of Dapagliflozin in Combination With Metformin on Body Weight in Subjects With Type2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Alone', 'orgStudyIdInfo': {'id': 'D1690C00012'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'A', 'description': 'Dapagliflozin 10 mg plus Metformin', 'interventionNames': ['Drug: Dapagliflozin', 'Drug: Metformin', 'Drug: Sitagliptin']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'B', 'description': 'Placebo plus Metformin', 'interventionNames': ['Drug: Metformin', 'Drug: Sitagliptin', 'Drug: Placebo']}], 'interventions': [{'name': 'Dapagliflozin', 'type': 'DRUG', 'description': 'Tablet oral 10 mg total daily dose once daily 102 weeks', 'armGroupLabels': ['A']}, {'name': 'Metformin', 'type': 'DRUG', 'description': 'Tablet oral 1500 - 2500 mg total daily dose 1-3 times a day104 weeks', 'armGroupLabels': ['A', 'B']}, {'name': 'Sitagliptin', 'type': 'DRUG', 'description': 'Tablet oral 100 mg total daily dose once daily rescue medication', 'armGroupLabels': ['A', 'B']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Matching placebo for dapagliflozin, tablet, oral, once daily, 102 weeks', 'armGroupLabels': ['B']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Blagoevgrad', 'country': 'Bulgaria', 'facility': 'Research Site', 'geoPoint': {'lat': 42.01457, 'lon': 23.09804}}, {'city': 'Sofia', 'country': 'Bulgaria', 'facility': 'Research Site', 'geoPoint': {'lat': 42.69751, 'lon': 23.32415}}, {'city': 'Beroun', 'country': 'Czechia', 'facility': 'Research Site', 'geoPoint': {'lat': 49.96382, 'lon': 14.072}}, {'city': 'Brno', 'country': 'Czechia', 'facility': 'Research Site', 'geoPoint': {'lat': 49.19522, 'lon': 16.60796}}, {'city': 'Prague', 'country': 'Czechia', 'facility': 'Research Site', 'geoPoint': {'lat': 50.08804, 'lon': 14.42076}}, {'city': 'Semily', 'country': 'Czechia', 'facility': 'Research Site', 'geoPoint': {'lat': 50.60191, 'lon': 15.33552}}, {'city': 'Slaný', 'country': 'Czechia', 'facility': 'Research Site', 'geoPoint': {'lat': 50.23046, 'lon': 14.08693}}, {'city': 'Balatonfüred', 'country': 'Hungary', 'facility': 'Research Site', 'geoPoint': {'lat': 46.96188, 'lon': 17.87187}}, {'city': 'Budapest', 'country': 'Hungary', 'facility': 'Research Site', 'geoPoint': {'lat': 47.49835, 'lon': 19.04045}}, {'city': 'Csongrád', 'country': 'Hungary', 'facility': 'Research Site', 'geoPoint': {'lat': 46.71332, 'lon': 20.14241}}, {'city': 'Kecskemét', 'country': 'Hungary', 'facility': 'Research Site', 'geoPoint': {'lat': 46.90618, 'lon': 19.69128}}, {'city': 'Tát', 'country': 'Hungary', 'facility': 'Research Site', 'geoPoint': {'lat': 47.74148, 'lon': 18.64813}}, {'city': 'Elblag', 'country': 'Poland', 'facility': 'Research Site', 'geoPoint': {'lat': 54.1522, 'lon': 19.40884}}, {'city': 'Krakow', 'country': 'Poland', 'facility': 'Research Site', 'geoPoint': {'lat': 50.06143, 'lon': 19.93658}}, {'city': 'Torun', 'country': 'Poland', 'facility': 'Research Site', 'geoPoint': {'lat': 53.01375, 'lon': 18.59814}}, {'city': 'Gothenburg', 'country': 'Sweden', 'facility': 'Research Site', 'geoPoint': {'lat': 57.70716, 'lon': 11.96679}}, {'city': 'Jarfalla', 'country': 'Sweden', 'facility': 'Research Site'}, {'city': 'Lund', 'country': 'Sweden', 'facility': 'Research Site', 'geoPoint': {'lat': 55.70584, 'lon': 13.19321}}, {'city': 'Malmo', 'country': 'Sweden', 'facility': 'Research Site', 'geoPoint': {'lat': 55.60587, 'lon': 13.00073}}, {'city': 'Stockholm', 'country': 'Sweden', 'facility': 'Research Site', 'geoPoint': {'lat': 59.32938, 'lon': 18.06871}}, {'city': 'Uppsala', 'country': 'Sweden', 'facility': 'Research Site', 'geoPoint': {'lat': 59.85882, 'lon': 17.63889}}], 'overallOfficials': [{'name': 'Jan Bolinder, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Dept of Endocrinology, Metabolism and Diabetes Karolinska University Hospital Huddinge Karolinska Institutet 141 86 Stockholm Sweden'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'AstraZeneca', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Bristol-Myers Squibb', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}