Ignite Creation Date:
2025-12-25 @ 2:02 AM
Ignite Modification Date:
2026-03-10 @ 6:18 PM
Study NCT ID:
NCT01483560
Status:
COMPLETED
Last Update Posted:
2019-06-19
First Post:
2011-11-23
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
REducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003922', 'term': 'Diabetes Mellitus, Type 1'}, {'id': 'D012164', 'term': 'Retinal Diseases'}], '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': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D005128', 'term': 'Eye Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008687', 'term': 'Metformin'}], 'ancestors': [{'id': 'D001645', 'term': 'Biguanides'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'John.Petrie@glasgow.ac.uk', 'phone': '+44 141 330', 'title': 'Prof John Petrie', 'phoneExt': '3325', 'organization': 'University of Glasgow'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'Adverse event data collected from the date of consent until 30 days post last IMP dose, an average of 3 years.', 'description': 'Definition used same as clinical trials.gov', 'eventGroups': [{'id': 'EG000', 'title': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily\n\nMetformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group', 'otherNumAtRisk': 219, 'deathsNumAtRisk': 219, 'otherNumAffected': 112, 'seriousNumAtRisk': 219, 'deathsNumAffected': 5, 'seriousNumAffected': 34}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo', 'otherNumAtRisk': 209, 'deathsNumAtRisk': 209, 'otherNumAffected': 52, 'seriousNumAtRisk': 209, 'deathsNumAffected': 2, 'seriousNumAffected': 31}], 'otherEvents': [{'term': 'Gastrointestinal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 88, 'numAffected': 88}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 18, 'numAffected': 18}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Cardiovascular', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Neurological', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hypersensitivity to Metformin', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 5, 'numAffected': 1}], 'organSystem': 'Product Issues', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Opthalmic adverse events', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 18, 'numAffected': 18}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 32, 'numAffected': 32}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Metabolic and nutrition', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 8, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Infections and Infestations', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Neoplasms', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 6, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Cerebral haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Gastrointestinal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Respiratory', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Cardiac', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 6, 'numAffected': 6}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Injury', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Coronary artery bypass graft', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Musculoskeletal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Sudden Death', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Angiogram', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Circulatory collapse', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Blood and Lymphatic', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Immune System Disorder', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Immune system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Cerebrovascular accident', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'hypoglycaemic coma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Transient Ischaemic Attack', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'lung lobectomy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'coronary stent insertion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Amputation revision', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Surgery (unspecified)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Coronary angioplasty', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Spinal fusion Surgery', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Aortic valve repair', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Chest Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Blood Glucose Fluctuation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Ischaemic Necrosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Peripheral Ischaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 219, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 209, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change in Averaged Mean Far Wall Common Carotid Artery Intima-media Thickness (cIMT)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '193', 'groupId': 'OG000'}, {'value': '194', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily\n\nMetformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '0.773', 'spread': '0.14', 'groupId': 'OG000'}, {'value': '0.791', 'spread': '0.183', 'groupId': 'OG001'}]}]}, {'title': '12 Months', 'categories': [{'measurements': [{'value': '0.782', 'spread': '0.147', 'groupId': 'OG000'}, {'value': '0.788', 'spread': '0.174', 'groupId': 'OG001'}]}]}, {'title': '24 Months', 'categories': [{'measurements': [{'value': '0.792', 'spread': '0.145', 'groupId': 'OG000'}, {'value': '0.823', 'spread': '0.187', 'groupId': 'OG001'}]}]}, {'title': '36 Months', 'categories': [{'measurements': [{'value': '0.793', 'spread': '0.134', 'groupId': 'OG000'}, {'value': '0.820', 'spread': '0.177', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '0, 12 months, 24 months, 36 months', 'description': "Progression of averaged mean far wall common carotid artery intima media thickness IMT (mean cIMT) measured using B mode ultrasonography with a 7.0 MHz or higher broadband linear array transducer and concurrent recording of 3-lead electrocardiogram (ECG). Longitudinal images of the common carotid artery will be obtained at anterior, lateral and posterior angles at baseline, 12, 24 and 36 months using Meijer's arc to standardize the transducer angle.", 'unitOfMeasure': 'mm', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in HbA1c', 'denoms': [{'units': 'Participants', 'counts': [{'value': '193', 'groupId': 'OG000'}, {'value': '194', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily\n\nMetformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '8.1', 'spread': '0.9', 'groupId': 'OG000'}, {'value': '8.0', 'spread': '0.8', 'groupId': 'OG001'}]}]}, {'title': '36 Months', 'categories': [{'measurements': [{'value': '8.1', 'spread': '0.9', 'groupId': 'OG000'}, {'value': '8.1', 'spread': '0.8', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, Year 3', 'description': 'Measured in accredited local laboratories participating in DCCT-aligned quality control programmes.', 'unitOfMeasure': '%units', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in LDL Cholesterol', 'denoms': [{'units': 'Participants', 'counts': [{'value': '193', 'groupId': 'OG000'}, {'value': '194', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily\n\nMetformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '2.23', 'spread': '0.7', 'groupId': 'OG000'}, {'value': '2.25', 'spread': '0.72', 'groupId': 'OG001'}]}]}, {'title': '36 Months', 'categories': [{'measurements': [{'value': '2.07', 'spread': '0.83', 'groupId': 'OG000'}, {'value': '2.21', 'spread': '0.71', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, Year 3', 'description': 'mmol/L Centrally assayed at the University of Glasgow', 'unitOfMeasure': 'mmol/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Estimated Glomerular Filtration Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '193', 'groupId': 'OG000'}, {'value': '194', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily\n\nMetformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '92.9', 'spread': '20.9', 'groupId': 'OG000'}, {'value': '91.1', 'spread': '21.6', 'groupId': 'OG001'}]}]}, {'title': '36 Months', 'categories': [{'measurements': [{'value': '92.1', 'spread': '20.8', 'groupId': 'OG000'}, {'value': '87.2', 'spread': '19.6', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, Year 1, Year 2, Year 3', 'description': 'Number of participants developing new microalbuminuria; change in absolute concentration Calculated using the MDRD equation1 based on creatinine measured in accredited local laboratories', 'unitOfMeasure': 'ml/min/1.73m2', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Retinopathy and at Least a 2 Stage Progression in Retinopathy From Baseline to 36 Months', 'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'OG000'}, {'value': '209', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily\n\nMetformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '191', 'groupId': 'OG000'}, {'value': '190', 'groupId': 'OG001'}]}]}, {'title': '36 Months', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline, Year 3', 'description': 'Two color 45° field retinal photographs (fields 1 and 2) from each eye at 0 and 36 months graded at the University of Wisconsin Ocular Epidemiology Reading Center (OERC) using the modified Airlie House classification scheme and the Early Treatment Diabetic Retinopathy Severity scale.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Weight', 'denoms': [{'units': 'Participants', 'counts': [{'value': '193', 'groupId': 'OG000'}, {'value': '194', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily\n\nMetformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '83.9', 'spread': '15.4', 'groupId': 'OG000'}, {'value': '83.5', 'spread': '13.7', 'groupId': 'OG001'}]}]}, {'title': '36 Months', 'categories': [{'measurements': [{'value': '82.0', 'spread': '15.4', 'groupId': 'OG000'}, {'value': '83.2', 'spread': '13.8', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, Year 1, Year 2, Year 3', 'description': 'Measured at sites using calibrated weighing scales', 'unitOfMeasure': 'kg', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Insulin Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '193', 'groupId': 'OG000'}, {'value': '194', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily\n\nMetformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '0.36', 'spread': '0.26', 'groupId': 'OG000'}, {'value': '0.68', 'spread': '0.30', 'groupId': 'OG001'}]}]}, {'title': '36 Months', 'categories': [{'measurements': [{'value': '0.62', 'spread': '0.26', 'groupId': 'OG000'}, {'value': '0.67', 'spread': '0.30', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, Year 1, Year 2, Year 3', 'description': 'Units/ kg body weight Extracted by study nurses from the Study Diary and reported on the study CRF using dedicated fields', 'unitOfMeasure': 'units/kg', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Endothelial Function', 'denoms': [{'units': 'Participants', 'counts': [{'value': '193', 'groupId': 'OG000'}, {'value': '194', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily\n\nMetformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '2.28', 'spread': '0.74', 'groupId': 'OG000'}, {'value': '2.24', 'spread': '0.75', 'groupId': 'OG001'}]}]}, {'title': '36 Months', 'categories': [{'measurements': [{'value': '2.17', 'spread': '0.69', 'groupId': 'OG000'}, {'value': '2.24', 'spread': '0.73', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, Year 1, Year 3', 'description': 'In some centres (Arbitrary units) Reactive Hyperaemia Index using the ENDOPAT device (Itamar, Israel)', 'unitOfMeasure': 'RHI (Arbitrary units)', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily\n\nMetformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '219'}, {'groupId': 'FG001', 'numSubjects': '209'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '193'}, {'groupId': 'FG001', 'numSubjects': '194'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}, {'groupId': 'FG001', 'numSubjects': '15'}]}]}], 'preAssignmentDetails': '493 participants where enrolled and consented. All participants entered a 3 month Run In phase with placebo. Participants who remained eligible were randomly assigned to receive metformin or placebo for 3 years. 65 participants where ineligible to be randomized.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily\n\nMetformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '55.2', 'spread': '8.5', 'groupId': 'BG000'}, {'value': '55.8', 'spread': '8.8', 'groupId': 'BG001'}, {'value': '55.5', 'spread': '8.7', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '90', 'groupId': 'BG000'}, {'value': '85', 'groupId': 'BG001'}, {'value': '175', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '129', 'groupId': 'BG000'}, {'value': '124', 'groupId': 'BG001'}, {'value': '253', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race and Ethnicity Not Collected', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Race and Ethnicity were not collected from any participant.'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Canada', 'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '55', 'groupId': 'BG000'}, {'value': '55', 'groupId': 'BG001'}, {'value': '110', 'groupId': 'BG002'}]}]}, {'title': 'Netherlands', 'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '16', 'groupId': 'BG000'}, {'value': '15', 'groupId': 'BG001'}, {'value': '31', 'groupId': 'BG002'}]}]}, {'title': 'Denmark', 'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}]}, {'title': 'United Kingdom', 'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '112', 'groupId': 'BG000'}, {'value': '105', 'groupId': 'BG001'}, {'value': '217', 'groupId': 'BG002'}]}]}, {'title': 'Australia', 'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '32', 'groupId': 'BG000'}, {'value': '30', 'groupId': 'BG001'}, {'value': '62', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Diabetes Diagnosis Duration', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '33.4', 'spread': '11', 'groupId': 'BG000'}, {'value': '34.3', 'spread': '10.5', 'groupId': 'BG001'}, {'value': '33.85', 'spread': '10.75', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Existing Cardiovascular Disease', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '30', 'groupId': 'BG000'}, {'value': '22', 'groupId': 'BG001'}, {'value': '52', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Baseline HbA1c', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '64.8', 'groupId': 'BG000'}, {'value': '64.7', 'groupId': 'BG001'}, {'value': '64.75', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'mmol/mol'}, {'title': 'Daily Insulin Dose', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '0.63', 'groupId': 'BG000'}, {'value': '0.68', 'groupId': 'BG001'}, {'value': '0.66', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'units/kg'}, {'title': 'BMI', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '28.4', 'spread': '4.5', 'groupId': 'BG000'}, {'value': '28.5', 'spread': '4.1', 'groupId': 'BG001'}, {'value': '28.5', 'spread': '4.3', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg/m2', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Blood Pressure', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '130.5', 'spread': '15', 'groupId': 'BG000'}, {'value': '128.5', 'spread': '14.6', 'groupId': 'BG001'}, {'value': '129.5', 'spread': '14.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Systolic BP (mmHg)', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Total Cholesterol', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '4', 'spread': '0.88', 'groupId': 'BG000'}, {'value': '4', 'spread': '0.93', 'groupId': 'BG001'}, {'value': '4', 'spread': '0.91', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'mmol/L', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'eGFR', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '92.9', 'spread': '20.9', 'groupId': 'BG000'}, {'value': '91.1', 'spread': '21.6', 'groupId': 'BG001'}, {'value': '92', 'spread': '21.3', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'ml/min/1.73m2', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Diabetic Retinopathy', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '219', 'groupId': 'BG000'}, {'value': '209', 'groupId': 'BG001'}, {'value': '428', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '51', 'groupId': 'BG000'}, {'value': '58', 'groupId': 'BG001'}, {'value': '109', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2015-11-09', 'size': 2150543, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2018-09-12T03:35', 'hasProtocol': True}, {'date': '2017-04-07', 'size': 709303, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2018-09-12T03:44', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 493}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-12'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-06', 'completionDateStruct': {'date': '2017-04-18', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-06-04', 'studyFirstSubmitDate': '2011-11-23', 'resultsFirstSubmitDate': '2018-09-20', 'studyFirstSubmitQcDate': '2011-11-30', 'lastUpdatePostDateStruct': {'date': '2019-06-19', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2019-02-18', 'studyFirstPostDateStruct': {'date': '2011-12-01', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2019-06-03', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-03-19', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in Averaged Mean Far Wall Common Carotid Artery Intima-media Thickness (cIMT)', 'timeFrame': '0, 12 months, 24 months, 36 months', 'description': "Progression of averaged mean far wall common carotid artery intima media thickness IMT (mean cIMT) measured using B mode ultrasonography with a 7.0 MHz or higher broadband linear array transducer and concurrent recording of 3-lead electrocardiogram (ECG). Longitudinal images of the common carotid artery will be obtained at anterior, lateral and posterior angles at baseline, 12, 24 and 36 months using Meijer's arc to standardize the transducer angle."}], 'secondaryOutcomes': [{'measure': 'Change in HbA1c', 'timeFrame': 'Baseline, Year 3', 'description': 'Measured in accredited local laboratories participating in DCCT-aligned quality control programmes.'}, {'measure': 'Change in LDL Cholesterol', 'timeFrame': 'Baseline, Year 3', 'description': 'mmol/L Centrally assayed at the University of Glasgow'}, {'measure': 'Change in Estimated Glomerular Filtration Rate', 'timeFrame': 'Baseline, Year 1, Year 2, Year 3', 'description': 'Number of participants developing new microalbuminuria; change in absolute concentration Calculated using the MDRD equation1 based on creatinine measured in accredited local laboratories'}, {'measure': 'Number of Participants With Retinopathy and at Least a 2 Stage Progression in Retinopathy From Baseline to 36 Months', 'timeFrame': 'Baseline, Year 3', 'description': 'Two color 45° field retinal photographs (fields 1 and 2) from each eye at 0 and 36 months graded at the University of Wisconsin Ocular Epidemiology Reading Center (OERC) using the modified Airlie House classification scheme and the Early Treatment Diabetic Retinopathy Severity scale.'}, {'measure': 'Change in Weight', 'timeFrame': 'Baseline, Year 1, Year 2, Year 3', 'description': 'Measured at sites using calibrated weighing scales'}, {'measure': 'Change in Insulin Dose', 'timeFrame': 'Baseline, Year 1, Year 2, Year 3', 'description': 'Units/ kg body weight Extracted by study nurses from the Study Diary and reported on the study CRF using dedicated fields'}, {'measure': 'Change in Endothelial Function', 'timeFrame': 'Baseline, Year 1, Year 3', 'description': 'In some centres (Arbitrary units) Reactive Hyperaemia Index using the ENDOPAT device (Itamar, Israel)'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['REMOVAL', 'metformin', 'carotid IMT', 'LDL Cholesterol', 'endothelial function', 'retinopathy', 'HbA1c'], 'conditions': ['Diabetes Mellitus, Type 1']}, 'referencesModule': {'references': [{'pmid': '38837240', 'type': 'DERIVED', 'citation': 'El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.'}, {'pmid': '28615149', 'type': 'DERIVED', 'citation': 'Petrie JR, Chaturvedi N, Ford I, Brouwers MCGJ, Greenlaw N, Tillin T, Hramiak I, Hughes AD, Jenkins AJ, Klein BEK, Klein R, Ooi TC, Rossing P, Stehouwer CDA, Sattar N, Colhoun HM; REMOVAL Study Group. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017 Aug;5(8):597-609. doi: 10.1016/S2213-8587(17)30194-8. Epub 2017 Jun 11.'}]}, 'descriptionModule': {'briefSummary': 'The trial is conducted in the United Kingdom (UK), Australia, Canada, Denmark and the Netherlands. The aim is to test whether 3 years treatment with metformin added to titrated insulin therapy (towards target HbA1c 7.0%/53 mmol/mol) reduces atherosclerosis, as measured by progression of carotid intima-media thickness (cIMT), in adults with confirmed type 1 diabetes aged 40 years and over at increased risk for cardiovascular disease.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '40 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Type 1 Diabetes for five years or more\\*\n* Age 40 years or above\n* 7.0 =\\< HbA1c \\<10.0% (53 - 86 mmol/mol)\n\nAND 3 or more of the following ten CardioVascular Disease (CVD) risk factors:\n\n* BMI \\>27 kg/m\\^2\n* Current HbA1c \\>8.0% (64 mmol/mol)\n* Known CVD/peripheral vascular disease\n* Current smoker\n* Estimated glomerular filtration rate (eGFR) \\<90 ml/min per 1.73 m\\^3\n* Confirmed micro- or macroalbuminuria \\[according to local assays and reference ranges\\]\n* Hypertension (BP \\>=140/90 millimeters of mercury (mmHg) or established on antihypertensive treatment)\n* Dyslipidaemia \\[total cholesterol \\>=5.0 mmol/L (200 mg/dL);OR HDL cholesterol \\<1.20 mmol/L (46mg/dL) \\[MEN\\]; OR \\<1.30 mmol/L (50 mg/dL) \\[WOMEN\\]; or triglycerides \\>=1.7 mmol/L (150mg/dL); or established on lipid-lowering treatment)\\]\n* Strong family history of CVD (at least one parent, biological aunt/ uncle, or sibling with myocardial infarction or stroke aged \\<60 years)\n* Duration of diabetes \\> 20 years\n\nExclusion Criteria:\n\n* eGFR \\< 45 ml/min/1.73m2\n* woman of childbearing age not on effective contraception\n* Pregnancy and/or lactation\n* Acute coronary syndrome or Stroke/Transient Ischaemic Attack within the last three months\n* NYHA stage 3 or 4 heart failure\n* Significant hypoglycaemia unawareness\n* Impaired cognitive function/ unable to give informed consent\n* Previous carotid surgery/ inability to capture adequate carotid images\n* Estimated glomerular filtration \\< 45ml/min/1.73m\\^2 (MDRD)\n* Gastroparesis\n* History of lactic acidosis\n* Other contraindications to metformin (hepatic impairment, known hypersensitivity to metformin, acute illness such as dehydration, severe infection, shock, acute cardiac failure or suspected tissue hypoxia)\n* Any coexistent life threatening condition including prior diagnosis of cancer within two years\n* History of alcohol problem or drug abuse'}, 'identificationModule': {'nctId': 'NCT01483560', 'acronym': 'REMOVAL', 'briefTitle': 'REducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL)', 'organization': {'class': 'OTHER', 'fullName': 'University of Glasgow'}, 'officialTitle': 'Phase 3 Study of Metformin in Adults With Type 1 Diabetes', 'orgStudyIdInfo': {'id': 'GN10DI406'}, 'secondaryIdInfos': [{'id': '2011-000300-18', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Metformin', 'description': 'Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily', 'interventionNames': ['Drug: Metformin']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Metformin', 'type': 'DRUG', 'otherNames': ['Glucophage'], 'description': '3 years treatment duration', 'armGroupLabels': ['Metformin']}, {'name': 'Placebo', 'type': 'DRUG', 'description': '3 years duration', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Melbourne', 'country': 'Australia', 'facility': 'Royal Melbourne Hospital', 'geoPoint': {'lat': -37.814, 'lon': 144.96332}}, {'city': 'Melbourne', 'country': 'Australia', 'facility': "St Vincent's Hospital", 'geoPoint': {'lat': -37.814, 'lon': 144.96332}}, {'city': 'Sydney', 'country': 'Australia', 'facility': 'Royal Prince Albert Hospital', 'geoPoint': {'lat': -33.86785, 'lon': 151.20732}}, {'city': 'London', 'state': 'Ontario', 'country': 'Canada', 'facility': "St Joseph's Health Care", 'geoPoint': {'lat': 42.98339, 'lon': -81.23304}}, {'city': 'Ottawa', 'country': 'Canada', 'facility': 'Ottawa Hospital Riverside Campus', 'geoPoint': {'lat': 45.41117, 'lon': -75.69812}}, {'city': 'Gentofte Municipality', 'country': 'Denmark', 'facility': 'Steno Diabetes Centre', 'geoPoint': {'lat': 55.74903, 'lon': 12.54601}}, {'city': 'Maastricht', 'country': 'Netherlands', 'facility': 'Maastricht University Medical Centre', 'geoPoint': {'lat': 50.84833, 'lon': 5.68889}}, {'city': 'Aberdeen', 'country': 'United Kingdom', 'facility': 'Aberdeen Royal Infirmary', 'geoPoint': {'lat': 57.14369, 'lon': -2.09814}}, {'zip': 'KA6 6DX', 'city': 'Ayr', 'country': 'United Kingdom', 'facility': 'Ayr Hospital', 'geoPoint': {'lat': 55.46273, 'lon': -4.63393}}, {'zip': 'BS2 8HW', 'city': 'Bristol', 'country': 'United Kingdom', 'facility': 'University Hospitals Bristol', 'geoPoint': {'lat': 51.45523, 'lon': -2.59665}}, {'city': 'Dundee', 'country': 'United Kingdom', 'facility': 'Diabetes Support Unit, Ninewells Hospital and Medical School', 'geoPoint': {'lat': 56.46913, 'lon': -2.97489}}, {'city': 'Durham', 'country': 'United Kingdom', 'facility': 'University Hospital North Durham', 'geoPoint': {'lat': 54.77676, 'lon': -1.57566}}, {'city': 'Edinburgh', 'country': 'United Kingdom', 'facility': 'Edinburgh Royal Infirmary', 'geoPoint': {'lat': 55.95206, 'lon': -3.19648}}, {'city': 'Edinburgh', 'country': 'United Kingdom', 'facility': 'Edinburgh Western Infirmary', 'geoPoint': {'lat': 55.95206, 'lon': -3.19648}}, {'city': 'Exeter', 'country': 'United Kingdom', 'facility': 'Peninsula NIHR Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust', 'geoPoint': {'lat': 50.7236, 'lon': -3.52751}}, {'city': 'Glasgow', 'country': 'United Kingdom', 'facility': 'Stobhill Hospital, Diabetes Clinic', 'geoPoint': {'lat': 55.86515, 'lon': -4.25763}}, {'zip': 'GL1 3NN', 'city': 'Gloucester', 'country': 'United Kingdom', 'facility': 'Gloucestershire Royal Hospital', 'geoPoint': {'lat': 51.86568, 'lon': -2.2431}}, {'city': 'Hull', 'country': 'United Kingdom', 'facility': 'Michael White Diabetes Centre, Hull Royal Infirmary', 'geoPoint': {'lat': 53.7446, 'lon': -0.33525}}, {'city': 'Liverpool', 'country': 'United Kingdom', 'facility': 'Clinical Sciences Centre, University Hospital', 'geoPoint': {'lat': 53.41058, 'lon': -2.97794}}, {'city': 'London', 'country': 'United Kingdom', 'facility': 'Clinical Investigation Unit, International Centre for Circulatory Health, Imperial College Healthcare NHS Trust', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'city': 'Manchester', 'country': 'United Kingdom', 'facility': 'Wellcome Trust Clinical Research Facility, Manchester Royal Infirmary', 'geoPoint': {'lat': 53.48095, 'lon': -2.23743}}, {'city': 'Newcastle', 'country': 'United Kingdom', 'facility': 'Newcastle NIHR Clinical Research Facility, Royal Victoria Hospital', 'geoPoint': {'lat': 54.21804, 'lon': -5.88979}}, {'city': 'Plymouth', 'country': 'United Kingdom', 'facility': 'Diabetes Clinical Research Centre, Plymouth', 'geoPoint': {'lat': 50.37153, 'lon': -4.14305}}, {'city': 'Salford', 'country': 'United Kingdom', 'facility': 'Salford Royal NHS Foundation Trust', 'geoPoint': {'lat': 53.48771, 'lon': -2.29042}}], 'overallOfficials': [{'name': 'John Petrie, Prof', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Glasgow'}, {'name': 'Helen Colhoun, Prof', 'role': 'STUDY_DIRECTOR', 'affiliation': 'University of Dundee'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', 'description': 'Site specific participant data will be made available to the site PIs later in 2017, after the main publications.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Glasgow', 'class': 'OTHER'}, 'collaborators': [{'name': 'NHS Greater Glasgow and Clyde', 'class': 'OTHER'}, {'name': 'Juvenile Diabetes Research Foundation', 'class': 'OTHER'}, {'name': 'Imperial College London', 'class': 'OTHER'}, {'name': 'University of Wisconsin, Madison', 'class': 'OTHER'}, {'name': 'University of Dundee', 'class': 'OTHER'}, {'name': 'Merck Serono S.A., Geneva', 'class': 'INDUSTRY'}, {'name': 'Itamar-Medical, Israel', 'class': 'INDUSTRY'}, {'name': 'University of Western Ontario, Canada', 'class': 'OTHER'}, {'name': 'University of Melbourne', 'class': 'OTHER'}, {'name': 'Steno Diabetes Center Copenhagen', 'class': 'OTHER'}, {'name': 'Maastricht University Medical Center', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Clinical Professor in Diabetic Medicine', 'investigatorFullName': 'Prof John Petrie', 'investigatorAffiliation': 'University of Glasgow'}}}}