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Using Metformin to Reduce Heart Risks in Veterans with Prediabetes

CSP #2002 - Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes (VA-IMPACT)

Phase 4 Interventional VA Office of Research and Development · NCT02915198

This study tests if the diabetes drug metformin can help reduce the risk of heart attacks, strokes, and death in Veterans with prediabetes and heart disease.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment7410 (estimated)
Ages18 Years and up
SexAll
SponsorVA Office of Research and Development Federal
Locations40 sites (Phoenix, Arizona and 39 other locations)
Trial IDNCT02915198 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates are Veterans with pre-diabetes and established atherosclerotic cardiovascular disease.

Not a fit: Patients without pre-diabetes or those without established cardiovascular disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly reduce cardiovascular events and mortality in Veterans with pre-diabetes.

How similar studies have performed: Previous studies have shown promising results for metformin in similar populations, suggesting potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion 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 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 this trial is running

Phoenix, Arizona and 39 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Prediabetic StateAtherosclerosisMetforminHemoglobin A, GlycosylatedCoronary Artery DiseasePeripheral Arterial DiseaseCerebrovascular Disorders
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.