Using Metformin to Reduce Heart Risks in Veterans with Prediabetes

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial investigates whether metformin can lower the risk of death, heart attacks, and strokes in Veterans diagnosed with pre-diabetes and existing atherosclerotic cardiovascular disease. It is a multicenter, randomized, double-blind trial where participants are assigned to receive either metformin or a placebo. Eligible patients must meet specific criteria for pre-diabetes and have established cardiovascular disease. The study aims to provide insights into the effectiveness of metformin in improving cardiovascular outcomes in this high-risk population.

Why it matters

Who can join: the full rules

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 greater than 130 mg/dL measured between screening and randomization visits, or any plasma glucose 180 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

Where it's running

• Phoenix VA Health Care System, Phoenix, AZ
  Phoenix, Arizona, United States Recruiting
• Southern Arizona VA Health Care System, Tucson, AZ
  Tucson, Arizona, United States Recruiting
• Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR
  Little Rock, Arkansas, United States Recruiting
• VA Loma Linda Healthcare System, Loma Linda, CA
  Loma Linda, California, United States Recruiting
• VA Long Beach Healthcare System, Long Beach, CA
  Long Beach, California, United States Recruiting
• VA Palo Alto Health Care System, Palo Alto, CA
  Palo Alto, California, United States Recruiting

Study contacts

• Study coordinator: Gregory G Schwartz, PhD MD
• Email: Gregory.Schwartz@va.gov
• Phone: (720) 723-6070

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.