PREvention of CardIovascular and DiabEtic kidNey Disease in Type 2 Diabetes

Eligibility Criteria

• * Type 2 diabetes based on clinical diagnosis
• * HbA1c ≥6% measured within 12 months prior to screening
• * Secondary prevention cohort (at least 70% of cohort):
• * Age 40 to 80 years
• * Evidence of established atherosclerotic cardiovascular disease (ASCVD), as defined by one or more of the following
• * Coronary heart disease defined by at least one of the following: prior myocardial infarction, prior coronary percutaneous coronary intervention, ≥50% stenosis of a coronary artery documented by invasive or non-invasive imaging (including CT coronary angiography), positive stress test, or coronary artery calcium score \>400 Agatston units;
• * Cerebrovascular disease defined by at least one of the following: prior ischemic stroke, prior carotid revascularization procedure, carotid stenosis ≥ 50% documented by X-ray angiography, MR angiography, CT angiography, or Doppler ultrasound;
• * Symptomatic peripheral artery disease defined by at least one of the following: leg symptoms with an ABI ≤ 0.9, leg symptoms with imaging evidence of a stenosis ≥50% in a peripheral artery documented by X-ray angiography, MR angiography, CT angiography, or Doppler ultrasound, or prior amputation for atherosclerotic disease.
• * Primary prevention cohort (capped at 30% of cohort):
• * Age 60-80 years and at least 1 additional high-risk feature:
• * Cardiovascular risk factors/high-risk features:
• * Active smoking (combustible tobacco or marijuana)
• * HbA1c ≥ 8% measured within 12 months prior to screening. The most recent value available at the time of screening will be used for screening and to determine eligibility.
• * Stage 3a CKD, eGFR 45-59 ml/min/1.73m2 measured within 12 months prior to screening. The most recent value available at screening will be used for screening and to determine eligibility.
• * Willingness to be randomly assigned to medication class (SGLT2i or GLP-1 RA or both) and fill prescription through personal pharmacy benefit while having other medications adjusted for safety
• * Willingness to avoid starting a therapy in the alternative treatment group (e.g., if randomized to GLP-1 RA, avoid starting an SGLT2i) unless strongly recommended by the participant's usual care provider.
• * If taking one of the study medication classes, willingness to stop SGLT2i or GLP-1 RA and be randomly assigned to one of the two medication classes
• * Willingness to consent to data collection using the electronic health record and sign a medical release to obtain future medical records from other health care facilities
• * Known or suspected diabetes of other cause (type 1 diabetes, pancreatogenic diabetes, monogenic diabetes, etc.)
• * Any background diabetes medication regimen will be allowed in this pragmatic trial with the following proviso:
• * History of diabetic ketoacidosis
• * Active diabetic foot ulcer
• * History of pancreatitis
• * Heart failure as a primary reason for hospitalization within the past year
• * Known left ventricular ejection fraction \<40%
• * Known urinary albumin-to-creatinine ratio \>200 mg/g at screening
• * Estimated glomerular filtration rate (eGFR) less than 45 ml/min/1.73m2 measured within 12 months prior to screening. The most recent value available at screening will be used for screening and to determine eligibility.
• * Known inability to afford study medication through current insurance coverage.
• * If a woman of child-bearing potential, the patient or partner is unwilling to use birth control
• * Active treatment for cancer, planned treatment for cancer, or recent active cancer with likelihood of recurrence or progression, which, in the opinion of the site investigator, has a likelihood of recurrence that would interfere with study therapy prior to 2028
• * Treated cancer with no evidence of disease, no evidence of disease progression, and no planned change in therapy is allowed. Examples of allowable cancers include:
• * Breast cancer stable after active treatment, managed with long-term anti-estrogen therapy
• * Prostate cancer being observed
• * Stage 0 or 1 tumors status post resection or other definitive treatment
• * Other similarly stable cancer comorbidities
• * History of solid organ or bone marrow transplant
• * Allergy to SGLT2 inhibitor or GLP-1 receptor agonist