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.
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
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
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- 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.
40 sites in 1 country
United States40 sites, 38 recruiting
- 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
- Terminated
Jesse Brown VA Medical Center, Chicago, IL
Chicago, Illinois, 60612
- Active, not recruiting
Cincinnati VA Medical Center, Cincinnati, OH
Cincinnati, Ohio, 45220-2213
- 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
- Not yet recruiting
Lexington VA Medical Center, Lexington, KY
Lexington, Kentucky, 40502-2235
Dennis Karounos, MD, 859-233-4511 ext. 4430, Dennis.Karounos@va.gov
- 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
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.
- Conditions
- Prediabetic State, Atherosclerosis, Metformin
- 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 group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Participants 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 |
| Placebo | Placebo comparator | Participants 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.
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)
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
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
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.
- First posted26 Sep 2016 (estimated)
- Study start3 Apr 2023
- Primary completion28 Sep 2029 (estimated)
- Study completion28 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prediabetic StateStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Gregory G. Schwartz, PhD MD, Study chair, Rocky Mountain Regional VA Medical Center, Aurora, CO
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