Official Title: “A Randomised Placebo-Controlled Trial of Metformin on Progression of Carotid Atherosclerosis in Non-Diabetic Patients With Cardiovascular Disease Treated With Conventional Risk Reducing Agents”

Hypothesis: Treatment with metformin in overweight non-diabetic individuals with coronary heart disease and on standard cardiovascular risk reducing agents including statins will have a beneficial impact on carotid artery atherosclerosis compared to placebo.

Rationale: Once subjects have a heart attack, they remain at much higher than average risk of another heart attack and stroke, despite the best current therapies to lower their cholesterol and blood pressure and thin their blood. Many subjects with heart disease also have problems metabolising (i.e.

processing) sugar even if they do not have diabetes. There is some evidence that metformin, a drug which improves sugar metabolism, decreases the risk of future heart attacks in diabetic patients. However, whether metformin further reduces the risk of heart disease beyond established treatments in people without diabetes is unknown.

Method: The investigators will test the ability metformin, a drug with proven safety, to slow the progression of furring up (known as atherosclerosis) of blood vessels in non-diabetic subjects with heart disease. This will be achieved by treating 2 groups of subjects with metformin and placebo pills respectively. To measure atherosclerosis, the investigators will carry out ultrasound scans of the big blood vessels in the neck at the start of the study, after 1 year and after 2 years of therapy.The investigators will then be able to assess whether metformin has had a beneficial impact.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: August 2011

Intervention(s) in this Clinical Trial

• Drug: Metformin
  • White film-coated tablets, 850mg tablet twice daily, 2 years duration
• Drug: Placebo
  • White coated tablet; one tablet twice daily; 2 years duration

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Placebo Comparator: 2

Primary Measures

• Difference in progression of carotid intima-media thickness (measured in millimetres) between groups treated with metformin and placebo
  • Time Frame: 2 years
    Safety Issue?: No

Secondary Measures

• Correlation of HbA1C, t-PA, CRP, IL-6, HOMA-IR and ICAM-1 with change in carotid IMT in metformin- and placebo-treated groups will be evaluated.
  • Time Frame: 2 years
    Safety Issue?: No
• Difference in progression of carotid total plaque area (measured in square millimetres) between groups treated with metformin and placebo
  • Time Frame: 2 years
    Safety Issue?: No
• Difference in progression of carotid total plaque volume (measured in cubic millimetres) between groups treated with metformin and placebo
  • Time Frame: 2 years
    Safety Issue?: No

Inclusion Criteria:

• Proven coronary heart disease (prior acute coronary syndrome, prior CABG or angiographically proven CHD)
• Aged 35-75 years
• Elevated waist circumference as per the International Diabetes Foundation criteria (94 cm in men and 80 cm in women)
• All patients will be on statin

Exclusion Criteria:

• Pregnancy and/or lactation at screening
• Premenopausal woman not on contraception
• 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 [FPG] <
• 7.0 mmol/L at screening18)
• Screening results: HbA1C ≥ 7.0% and/or fasting plasma glucose ≥ 7.0 mmol/L
• Patients with Acute Coronary Syndrome within the last 3 months
• Clinically unstable heart failure
• Uncontrolled angina
• Contraindications to metformin

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 35 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Glasgow

Overall Clinical Trial Officials and Contacts

Naveed Sattar, PhD Principal Investigator University of Glasgow  

Overall Contact: Naveed Sattar, PhD +44 141 3303419 nsattar@clinmed.gla.ac.uk

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00723307

Study ID Number: Gla-Met-1

ClinicalTrials.gov Identifier: NCT00723307

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency