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

University of Glasgow

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: Placebo; Drug: Metformin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01483560

2011-000300-18 (EudraCT Number)

GN10DI406

Details and patient eligibility

About

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.

Enrollment: 493 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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493 participants in 2 patient groups, including a placebo group

Metformin

Experimental group

Description:

Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily

Treatment:

Drug: Metformin

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo