Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorVA Office of Research and Development
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
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.
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Metformin XR
DrugThe study medication dose may be increased by a step-wise fashion up to a maximum of 4 tablets per day.
Placebo
DrugFor 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
Treatment groups
7,410 Participants
are divided into 2 treatment groupsGroup A: MetforminExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
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.
Time frame
through study completion, an average of 4.5 yearsSecondary outcomes
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
Time frame
through study completion, an average of 4.5 years2
Time in days to Oncologic Outcome
Time to new or recurrent diagnosis of a malignancy or death from a malignancy
Time frame
through study completion, an average of 4.5 years3
Time in days to Diabetes Outcome
Time to new diagnosis of type 2 diabetes
Time frame
through study completion, an average of 4.5 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov