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Prediabetic StatePhase 4VA-IMPACTNCT02915198

Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes

A Phase 4 study testing Metformin XR in people with Prediabetic State and Atherosclerosis, run by VA Office of Research and Development at 40 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This research will help us to learn if the medicine called metformin reduces the risk of death, heart attacks, and/or strokes in Veterans who have pre-diabetes and heart or blood vessel problems. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Prediabetic State, Atherosclerosis, Metformin
What is being tested?
Metformin XR
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
7,410 participants
Where
40 sitesUnited States
Study dates
3 Apr 2023to 28 Sep 2029
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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):
  • History of myocardial infarction at least one month prior to randomization.
  • History of percutaneous coronary intervention or coronary artery bypass surgery at least one month prior to randomization.
  • Angiographic evidence of coronary stenosis of at least 50% in at least two major epicardial coronary arteries.
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  • Cerebrovascular disease is fulfilled by at least one of criteria (1) through (4):
  • Documented prior ischemic stroke (at least one month prior to randomization),
  • Carotid artery stenosis 50% and history of transient ischemic attack or transient ischemic visual symptoms attributable to the identified lesion(s),
  • Asymptomatic carotid stenosis of at least 70% luminal diameter,
  • History of carotid revascularization (surgical or catheter-based).
  • Peripheral arterial disease: Fulfilled by at least one of the following:
  • History of aorto-iliac or peripheral artery intervention (surgical or catheter based) for limb ischemia, or amputation for limb ischemia,
  • 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.

Who cannot join

  • 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.
  • Treatment with systemic glucocorticoids within 3 months of randomization
  • 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.
  • Total CO2 below the local laboratory lower limit of normal on most recent blood chemistry panel
  • Current treatment with cimetidine, vandetanib, or a systemic treatment with a carbonic anhydrase inhibitor.
  • Cirrhosis, active hepatitis, or jaundice at time of randomization, or total bilirubin > 2 times upper limit of normal
Show all 18Show fewer
  • Binge or heavy alcohol consumption within 6 months of randomization
  • Severe anemia (hemoglobin < 10 g/dL)
  • Prior history of intolerance to metformin
  • Myocardial infarction, coronary revascularization procedure, or stroke within 1 month of randomization
  • Uncontrolled hypertension at screening assessment (systolic blood pressure 180 mm Hg or diastolic blood pressure 110 mm Hg
  • Acute or decompensated congestive heart failure
  • Expected survival less than study duration
  • Participants considered to be unable, unwilling, or unreliable to meet protocol requirements
  • Impaired decision-making capacity, defined by any history of dementia or cognitive impairment
  • Concurrent participation in another research study involving a randomized comparison of drug or device treatments, unless specifically excepted.
  • Pregnant, intent to become pregnant during the trial, or lactating
  • Women of childbearing potential who are not using a highly effective method of contraception

Trial locations and contacts

40 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Gregory G Schwartz, PhD MD contact

(720) 723-6070

Gregory.Schwartz@va.gov

Kevin Gropp contact

(720) 857-5659

kevin.gropp@va.gov

40 sites in 1 country

United States40 sites, 38 recruiting

  • New Mexico VA Health Care System, Albuquerque, NM

    Albuquerque, New Mexico, 87108-5153

    Michelle D Ratliff, MD, 505-265-1711 ext. 4495, Michelle.Ratliff@va.gov

    Recruiting

  • Rocky Mountain Regional VA Medical Center, Aurora, CO

    Aurora, Colorado, 80045-7211

    Sridharan Raghavan, MD PhD, (415) 254-3563, Sridharan.Raghavan@va.gov

    Gregory G. Schwartz, PhD MD

    Recruiting

  • Rehabilitation R&D Service, Baltimore, MD

    Baltimore, Maryland, 21202

    Ilias Spanakis, MD, 410-605-7000 ext. 7394, Ilias.Spanakis@va.gov

    Recruiting

  • Bay Pines VA Healthcare System, Pay Pines, FL

    Bay Pines, Florida, 33744-0000

    Manjunath Harlapur, MD, 727-398-6661 ext. 14893, Manjunath.Harlapur@va.gov

    Recruiting

  • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

    Boston, Massachusetts, 02130-4817

    Scott Kinlay, MD, 857-203-6840, Scott.Kinlay@va.gov

    Recruiting

  • Ralph H. Johnson VA Medical Center, Charleston, SC

    Charleston, South Carolina, 29401-5703

    Ashley Waring, MD, 843-789-6467, Ashley.Waring@va.gov

    Recruiting

  • Jesse Brown VA Medical Center, Chicago, IL

    Chicago, Illinois, 60612

    Terminated

  • Cincinnati VA Medical Center, Cincinnati, OH

    Cincinnati, Ohio, 45220-2213

    Active, not recruiting

  • Louis Stokes VA Medical Center, Cleveland, OH

    Cleveland, Ohio, 44106-1702

    Laure Sayyed Kassem, MD, 216-791-3800 ext. 65184, Laure.SayyedKassem@va.gov

    Recruiting

  • Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC

    Columbia, South Carolina, 29209-1638

    Subhashini Yaturu, MD, 803-776-4000 ext. 6092, Subhashini.Yaturu@va.gov

    Recruiting

  • VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

    Dallas, Texas, 75216-7167

    Colleen Sam, MD, 214-857-1477, Colleen.Sam@va.gov

    Recruiting

  • Atlanta VA Medical and Rehab Center, Decatur, GA

    Decatur, Georgia, 30033-4004

    Mary Rhee, MD, 404-321-6111 ext. 202080, Mary.Rhee@va.gov

    Recruiting

  • Durham VA Medical Center, Durham, NC

    Durham, North Carolina, 27705-3875

    Matthew Crowley, MD, 919-599-8865, Matthew.Crowley@va.gov

    Recruiting

  • North Florida/South Georgia Veterans Health System, Gainesville, FL

    Gainesville, Florida, 32608-1135

    Carsten Schmalfuss, MD, 352-376-1611 ext. 6052, Carsten.Schmalfuss@va.gov

    Recruiting

  • Edward Hines Jr. VA Hospital, Hines, IL

    Hines, Illinois, 60141-3030

    Amit Dayal, MD, 708-202-8387 ext. 24564, Amit.Dayal@va.gov

    Recruiting

  • VA Pacific Islands Health Care System, Honolulu, HI

    Honolulu, Hawaii, 96819-1522

    Kelsey Shikuma-Lee, MD, 808-433-7643, Kelsey.ShikumaLee@va.gov

    Recruiting

  • Michael E. DeBakey VA Medical Center, Houston, TX

    Houston, Texas, 77030-4211

    Arunima Misra, MD, 713-791-1414 ext. 27940, Arunima.Misra@va.gov

    Recruiting

  • Huntington VA Medical Center, Huntington, WV

    Huntington, West Virginia, 25704-9300

    Tina Sias, MD, 304-429-6755 ext. 2580, Tina.Sias@va.gov

    Recruiting

  • Iowa City VA Health Care System, Iowa City, IA

    Iowa City, Iowa, 52246-2292

    David Katz, MD, 319-353-8622, David.Katz2@va.gov

    Recruiting

  • Kansas City VA Medical Center, Kansas City, MO

    Kansas City, Missouri, 64128-2226

    Mariana Garcia-Touza, MD, 914-886-3866, Mariana.Garcia-Touza@va.gov

    Recruiting

  • Lexington VA Medical Center, Lexington, KY

    Lexington, Kentucky, 40502-2235

    Dennis Karounos, MD, 859-233-4511 ext. 4430, Dennis.Karounos@va.gov

    Not yet recruiting

  • Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR

    Little Rock, Arkansas, 72205-5484

    Barry Uretsky, MD, 501-257-5808, Barry.Uretsky@va.gov

    Recruiting

  • VA Loma Linda Healthcare System, Loma Linda, CA

    Loma Linda, California, 92357-1000

    Geir Frivold, MD, 909-825-7084 ext. 3629, Geir.frivold@va.gov

    Recruiting

  • VA Long Beach Healthcare System, Long Beach, CA

    Long Beach, California, 90822

    Anthony Vo, MD, 562-826-3497, Anthony.Vo@va.gov

    Recruiting

  • Memphis VA Medical Center, Memphis, TN

    Memphis, Tennessee, 38104-2127

    Richard D Childress, MD, 901-523-8990 ext. 6817, richard.childress@va.gov

    Recruiting

  • Miami VA Healthcare System, Miami, FL

    Miami, Florida, 33125

    Ana Palacio, MD, 305-926-3780, Ana.Palacio@va.gov

    Recruiting

  • Clement J. Zablocki VA Medical Center, Milwaukee, WI

    Milwaukee, Wisconsin, 53295-0001

    Cynthia Kay, MD, 414-384-2000 ext. 42263, Cynthia.Kay@va.gov

    Recruiting

  • Minneapolis VA Health Care System, Minneapolis, MN

    Minneapolis, Minnesota, 55417-2309

    Selcuk Adabag, MD, 612-467-3655, Selcuk.Adabag@va.gov

    Recruiting

  • Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY

    New York, New York, 10010-5011

    Binita Shah, MD, 212-686-7500 ext. 7722, Binita.Shah@va.gov

    Recruiting

  • Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE

    Omaha, Nebraska, 68105-1850

    Cyrus Desouza, MD, 402-346-8800 ext. 5506, cyrus.desouza@va.gov

    Recruiting

  • VA Palo Alto Health Care System, Palo Alto, CA

    Palo Alto, California, 94304-1207

    Arlina Ahluwalia, MD, 650-493-5000 ext. 61755, Arlina.Ahluwalia@va.gov

    Paul Heidenreich, MD, 6504935000 ext. 64069, Paul.Heidenreich@va.gov

    Recruiting

  • Phoenix VA Health Care System, Phoenix, AZ

    Phoenix, Arizona, 85012

    Peter Reaven, MD, 602-277-5551 ext. 6875, Peter.Reaven@va.gov

    Recruiting

  • VA Portland Health Care System, Portland, OR

    Portland, Oregon, 97207-2964

    North Noelck, MD, 503-220-8262 ext. 56426, North.Noelck2@va.gov

    Linda Humphrey, MD, 5032208262 ext. 57176, Linda.Humphrey@va.gov

    Recruiting

  • Hunter Holmes McGuire VA Medical Center, Richmond, VA

    Richmond, Virginia, 23249

    Edward McFalls, MD, 804-675-5419, Edward.McFalls@va.gov

    Recruiting

  • Salem VA Medical Center, Salem, VA

    Salem, Virginia, 24153-6404

    Ali Iranmanesh, MD, 540-983-1071, Ali.Iranmanesh@va.gov

    Recruiting

  • VA Salt Lake City Health Care System, Salt Lake City, UT

    Salt Lake City, Utah, 84148-0001

    Charles Lui, MD, 801-582-1565, Charles.Lui@va.gov

    Recruiting

  • VA San Diego Healthcare System, San Diego, CA

    San Diego, California, 92161-0002

    Leda Felicio, MD, 858-552-8585 ext. 2232, leda.felicio@va.gov

    Recruiting

  • Southern Arizona VA Health Care System, Tucson, AZ

    Tucson, Arizona, 85723-0001

    Punit Goel, MD, 520-792-1450 ext. 16445, Punit.Goel@va.gov

    Recruiting

  • VA Connecticut Healthcare System West Haven Campus, West Haven, CT

    West Haven, Connecticut, 06516-2770

    Brian Malm, MD, 203-932-5711 ext. 2650, Brian.Malm@va.gov

    Recruiting

  • VA Greater Los Angeles Healthcare System, West Los Angeles, CA

    West Los Angeles, California, 90073-1003

    Tannaz Moin, MD, 310-478-3711 ext. 48380, Tannaz.Moin@va.gov; tmoin@mednet.ucla.edu

    Recruiting

Other trials in United States

About this study

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

This research will help us to learn if the medicine called metformin reduces the risk of death, heart attacks, and/or strokes in Veterans who have pre-diabetes and heart or blood vessel problems.

Read the detailed description

CSP #2002 is a multicenter, prospective, randomized, double blind, secondary prevention trial to test the hypothesis that treatment with metformin, compared with placebo, reduces mortality and cardiovascular morbidity in Veterans with pre-diabetes and established atherosclerotic cardiovascular disease. Qualifying patients have pre-diabetes defined by HbA1c, fasting blood glucose, or oral glucose tolerance test criteria; clinically evident coronary, cerebrovascular, or peripheral arterial atherosclerotic cardiovascular disease; and estimated glomerular filtration rate of at least 45 mL/min/1.73 m2; and do not fulfill any exclusion criteria. Patients who are eligible and agree to participate are randomly assigned to treatment with metformin XR (titrated to a maximum dose of 2000 mg daily based on safety and tolerability) or matching placebo. All patients receive counseling on therapeutic lifestyle recommendations.

CSP #2002 had a Pilot Phase trial from 2/2019 to 1/2021 and was approved for the full-scale trial, with Full-scale study launch in 04/2023.

Being tested
Metformin XR, Placebo
Keywords
Metformin, Atherosclerosis, Prediabetic State, Hemoglobin A, Glycosylated, Coronary Artery Disease, Peripheral Arterial Disease, Cerebrovascular Disorders
Medical subject headings
Prediabetic State, Atherosclerosis, Coronary Artery Disease, Peripheral Arterial Disease, Cerebrovascular Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Metformin XRDrug

    The study medication dose may be increased by a step-wise fashion up to a maximum of 4 tablets per day.

  • PlaceboDrug

    For patients < 80 years of age at the time of a study visit, and with most recent eGFR 45 mL/min/1.73 m2, study medication dose may be increased in a stepwise fashion to a maximum of 4 tablets daily, corresponding to metformin XR 2000 mg or matching placebo.

    For patients 80 years of age or with most recent 30 eGFR < 45 mL/min/1.73 m2, the maximum dose of study medication is 2 tablets daily, corresponding to metformin XR 1000 mg or matching placebo

Study groups in NCT02915198
Study groupRoleWhat they receive
MetforminExperimentalParticipants receive initial treatment with metformin XR 500 mg 1 tablet daily, with stepwise titration to a maximum dose of 2000 mg (4 tablets) daily.
Receives: Drug: Metformin XR
PlaceboPlacebo comparatorParticipants receive initial treatment with 1 tablet daily of placebo (for metformin XR), with stepwise titration to a maximum of 4 tablets daily.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time in days to death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina, or symptom-driven coronary revascularization

    The primary outcome measure is the time to first occurrence of death, non-fatal myocardial infarction or stroke, hospitalization for unstable angina with objective evidence of acute myocardial ischemia, or coronary revascularization driven by acute or progressive symptoms.

    Measured: through study completion, an average of 4.5 years

Secondary outcomes (3)

  1. Time in days to Cardiovascular Outcomes

    • Time to first occurrence of death, myocardial infarction, or stroke
    • Time to first occurrence of a primary endpoint event, peripheral arterial disease event, or hospitalization for congestive heart failure
    • Cumulative incidence of all components of the primary endpoint, including recurrent or multiple events in the same participant
    • Cumulative incidence and time to first occurrence of each component of the primary outcome measure, peripheral arterial disease events, and hospitalization for congestive heart failure

    Measured: through study completion, an average of 4.5 years

  2. Time in days to Oncologic Outcome

    Time to new or recurrent diagnosis of a malignancy or death from a malignancy

    Measured: through study completion, an average of 4.5 years

  3. Time in days to Diabetes Outcome

    Time to new diagnosis of type 2 diabetes

    Measured: through study completion, an average of 4.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2016 (estimated)
  2. Study start3 Apr 2023
  3. Primary completion28 Sep 2029 (estimated)
  4. Study completion28 Sep 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
7,410 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02915198
Sponsor's protocol ID
2002
Acronym
VA-IMPACT
Status last verified
Dec 2025
First submitted
13 Sep 2016
Last updated
17 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Metformin XR in people with Prediabetic State and Atherosclerosis, run by VA Office of Research and Development at 40 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Gregory G Schwartz, PhD MD ((720) 723-6070, Gregory.Schwartz@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time in days to death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina, or symptom-driven coronary revascularization (time frame: through study completion, an average of 4.5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02915198.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.

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