Title
REducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL)
Phase 3 Study of Metformin in Adults With Type 1 Diabetes
Phase
Phase 3Lead Sponsor
University of GlasgowStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Diabetes Mellitus, Type 1Intervention/Treatment
sitagliptin ...Study Participants
493The 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.
3 years treatment duration
3 years duration
Inclusion Criteria: Type 1 Diabetes for five years or more* Age 40 years or above 7.0 =< HbA1c <10.0% (53 - 86 mmol/mol) AND 3 or more of the following ten CardioVascular Disease (CVD) risk factors: BMI >27 kg/m^2 Current HbA1c >8.0% (64 mmol/mol) Known CVD/peripheral vascular disease Current smoker Estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m^3 Confirmed micro- or macroalbuminuria [according to local assays and reference ranges] Hypertension (BP >=140/90 millimeters of mercury (mmHg) or established on antihypertensive treatment) 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)] Strong family history of CVD (at least one parent, biological aunt/ uncle, or sibling with myocardial infarction or stroke aged <60 years) Duration of diabetes > 20 years Exclusion Criteria: eGFR < 45 ml/min/1.73m2 woman of childbearing age not on effective contraception Pregnancy and/or lactation Acute coronary syndrome or Stroke/Transient Ischaemic Attack within the last three months NYHA stage 3 or 4 heart failure Significant hypoglycaemia unawareness Impaired cognitive function/ unable to give informed consent Previous carotid surgery/ inability to capture adequate carotid images Estimated glomerular filtration < 45ml/min/1.73m^2 (MDRD) Gastroparesis History of lactic acidosis 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) Any coexistent life threatening condition including prior diagnosis of cancer within two years History of alcohol problem or drug abuse
| Event Type | Organ System | Event Term | Metformin | Placebo |
|---|
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.
Measured in accredited local laboratories participating in DCCT-aligned quality control programmes.
mmol/L Centrally assayed at the University of Glasgow
Number of participants developing new microalbuminuria; change in absolute concentration Calculated using the MDRD equation1 based on creatinine measured in accredited local laboratories
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.
Measured at sites using calibrated weighing scales
Units/ kg body weight Extracted by study nurses from the Study Diary and reported on the study CRF using dedicated fields
In some centres (Arbitrary units) Reactive Hyperaemia Index using the ENDOPAT device (Itamar, Israel)
