Participants must have definite coronary heart disease: either a previous myocardial infarction or positive findings on coronary angiogram. They can have normal glucose tolerance, impaired fasting glycaemia or impaired glucose tolerance but must not be diabetic. Participants will also be overweight as defined by a waist circumference >80cm in women and >94cm in men. MedDRA version: 9.1 Level: LLT Classification code 10051615 Term:
Conditions
Interventions
Trade Name: Glucophage 850mg film-coated tablet (metformin hydrochloride)
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Film-coated tablet
Sponsors
Greater Glasgow Health Board, Research and Development Department
Senior Contracts Manager,Research and Enterprise,University of Glasgow
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: o Proven coronary heart disease (prior acute coronary syndrome, prior coronary artery bypass graft or angiographically proven coronary heart disease) o Aged 35-75 years o Elevated waist circumference as per the International Diabetes Foundation criteria (94cm in men and 80cm in women) o Attending Cardiology outpatient clinics at Glasgow Royal Infirmary, the Western Infirmary, Stobhill Hospital and Royal Alexandra Hospital ; and patients identified at volunteering GP surgeries in Glasgow as approved by the Scottish Primary Care Research Network o All patients will be on statin medication. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: o Pregnancy and/or lactation at screening o Premenopausal woman not on adequate contraception (defined as daily oral hormonal contraception or regular injectable hormonal contraception) o Known or newly diagnosed diabetes mellitus on oral glucose tolerance testing (OGTT will be performed on subjects with HbA1C 6.0-6.9% and fasting plasma glucose <7.0mmol/L at screening) o Screening results: HbA1C =7.0% and/or fasting plasma glucose =7.0mmol/L o Patients with acute coronary syndrome within the last 3 months o Stage 3 or 4 heart failure defined according to the New York Heart Association criteria o Uncontrolled angina o Contraindications to metformin (example hepatic impairment, renal impairment [eGFR <45 mL/min/1.73m2 at screening], known hypersensitivity to metformin, acute illness [dehydration, severe infection, shock, acute cardiac failure]), and suspected tissue hypoxia will be excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Comparison of change in distal common carotid intima media thickness, as measured in millimetres by carotid ultrasound between baseline and 1.5 years, in two groups treated with placebo or metformin 850mg bd.; Main Objective: To examine in a double blind placebo controlled randomised trial whether metformin (Glucophage 850mg bd) therapy attenuates carotid atherosclerosis in overweight, non-diabetic (including normal and impaired glucose tolerance) patients with proven cardiovascular disease who are adequately treated statin therapy. Carotid atherosclerosis will be assessed by ultrasound measurement of distal common carotid intima media thickness on 3 occasions over 1.5 years for each subject. Primary outcome measure: comparison of change in carotid intima-media thickness (measured in mm) over 1.5 years between metformin- and placebo-treated groups. ; Secondary Objective: We will analyse whether change in carotid atherosclerosis correlates with improvements in Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), HbA1C, lipid subfractions, t-PA, CRP, IL-6 and ICAM-1 using appropriate blood tests. Furthermore, we will assess any change in two dimensional plaque area, total plaque count and total plaque volume over 1.5 years. | — |
Countries
United Kingdom
Outcome results
None listed