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

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 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 <90 ml/min per 1.73 m^3
• Confirmed micro- or macroalbuminuria [according to local assays and reference ranges]
• Hypertension (BP >=140/90mmHg 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