REducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL)
REducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL)
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.
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