Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes

Launched by VA OFFICE OF RESEARCH AND DEVELOPMENT · Sep 22, 2016

Keywords

ClinConnect Summary

This clinical trial is studying whether the medication metformin can help reduce the risk of serious heart problems, like heart attacks and strokes, in veterans who have pre-diabetes and existing heart or blood vessel issues. Pre-diabetes means that your blood sugar levels are higher than normal but not high enough to be classified as diabetes. To participate in this study, you need to have specific heart-related conditions, such as a history of heart attacks or strokes, and meet certain blood sugar level criteria.

If you qualify and choose to join the study, you will be monitored to see how well metformin works for your heart health over time. Participants will be required to follow the study's procedures and may need to attend regular check-ups. It's important to note that this study is currently looking for participants aged 65 to 74, and those who have not taken metformin or other diabetes medications recently may be eligible. This research could provide valuable insights into how metformin might help improve heart health in people with pre-diabetes.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Pre-diabetes: This condition is fulfilled by HbA1c of at least 5.7%, but less than 6.5%; or two measurements of fasting plasma glucose (on separate days) of 100-125 mg/dL; or a 2-hour plasma glucose level of 140-199 mg/dL following a 75 g glucose load oral glucose tolerance test.
• • 2. Established atherosclerotic cardiovascular disease: Qualifying participants must have evidence of atherosclerotic disease in at least one of the following vascular beds: coronary, cerebrovascular, or peripheral arterial circulation.
• Coronary artery disease is fulfilled by at least one of (1), (2), or (3):
• • 1. History of myocardial infarction at least one month prior to randomization.
• • 2. History of percutaneous coronary intervention or coronary artery bypass surgery at least one month prior to randomization.
• • 3. Angiographic evidence of coronary stenosis of at least 50% in at least two major epicardial coronary arteries.
• Cerebrovascular disease is fulfilled by at least one of criteria (1) through (4):
• • 1. Documented prior ischemic stroke (at least one month prior to randomization),
• • 2. Carotid artery stenosis 50% and history of transient ischemic attack or transient ischemic visual symptoms attributable to the identified lesion(s),
• • 3. Asymptomatic carotid stenosis of at least 70% luminal diameter,
• • 4. History of carotid revascularization (surgical or catheter-based).
• Peripheral arterial disease: Fulfilled by at least one of the following:
• • 1. History of aorto-iliac or peripheral artery intervention (surgical or catheter based) for limb ischemia, or amputation for limb ischemia,
• • 2. Symptoms of intermittent claudication with ankle:brachial index less than or equal to 0.85.
• • 3. Renal function: Estimated glomerular filtration rate at least 45 mL/min/1.73 m2.
• • 4. Informed consent has been fully executed, and participant agrees to study procedures.
• Exclusion Criteria:
• • 1. Treatment with metformin or other anti-diabetic medication within 12 months of randomization. Note: In the absence of a diagnosis of diabetes, inpatient treatment with insulin or treatment with an SGLT2 inhibitor (e.g., for heart failure) or a GLP-1 receptor agonist (e.g., for obesity) is not exclusionary.
• • 2. Treatment with systemic glucocorticoids within 3 months of randomization
• • 3. Fasting plasma glucose 140 mg/dL measured between screening and randomization visits, or any plasma glucose 200 mg/dL or HbA1c 7.0% measured within 12 months of randomization.
• • 4. Total CO2 below the local laboratory lower limit of normal on most recent blood chemistry panel
• • 5. Current treatment with cimetidine, vandetanib, or a systemic treatment with a carbonic anhydrase inhibitor.
• • 6. Cirrhosis, active hepatitis, or jaundice at time of randomization, or total bilirubin \> 2 times upper limit of normal
• • 7. Binge or heavy alcohol consumption within 6 months of randomization
• • 8. Severe anemia (hemoglobin \< 10 g/dL)
• • 9. Prior history of intolerance to metformin
• • 10. Myocardial infarction, coronary revascularization procedure, or stroke within 1 month of randomization
• • 11. Uncontrolled hypertension at screening assessment (systolic blood pressure 180 mm Hg or diastolic blood pressure 110 mm Hg
• • 12. Acute or decompensated congestive heart failure
• • 13. Expected survival less than study duration
• • 14. Participants considered to be unable, unwilling, or unreliable to meet protocol requirements
• • 15. Impaired decision-making capacity, defined by any history of dementia or cognitive impairment
• • 16. Concurrent participation in another research study involving a randomized comparison of drug or device treatments, unless specifically excepted.
• • 17. Pregnant, intent to become pregnant during the trial, or lactating
• • 18. Women of childbearing potential who are not using a highly effective method of contraception