Inclusion Criteria

• Age ≥ 45 years at screening.

• BMI of ≥ 27.0 kg/m^2 at screening.

• History of Atherosclerotic Cardiovascular Disease (ASCVD) with a documented history of at least one of the following:

  • Prior MI (presumed atherothrombotic event due to plaque rupture/erosion).
  • Prior ischemic stroke (presumed due to atherosclerosis; may include ischemic stroke with hemorrhagic transformation).
  • Symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) < 0.9 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease.

Exclusion Criteria

• History of any of the following within 60 days before screening or between screening and randomization: MI, hospitalization for unstable angina, arterial revascularization (eg, coronary, cerebrovascular or peripheral) major cardiovascular surgery, stroke, or transient ischemic attack (TIA).

• New York Heart Association (NYHA) class IV HF during screening or hospitalization for HF within 60 days before screening or between screening and randomization.

• Type 1 DM, or any other type of diabetes with the exception of T2DM or prior gestational diabetes. Participants with a history of gestational diabetes should be stratified according to their current diabetes classification.

• For participants with T2DM (including those without a prior history of T2DM but with a HbA1c ≥ 6.5% during screening):

  • HbA1c > 10.0% (86 mmol/mol) at screening.
  • History of diabetic ketoacidosis or hyperosmolar state/coma within 12 months before randomization.
  • One or more episodes of severe hypoglycemia within 6 months before randomization and/or history of hypoglycemia unawareness.
  • History of proliferative diabetic retinopathy, diabetic maculopathy, severe non-proliferative diabetic retinopathy, or currently receiving or planning to receive treatment for diabetic retinopathy and/or diabetic macular edema.

• Use of any glucagon-like peptide-1 receptor agonist (GLP-1 RA), glucose-dependent insulinotropic polypeptide (GIP) agonists or antagonists, or amylin analogs within 90 days before randomization or planned use during the conduct of the trial.

• History of chronic pancreatitis or history of acute pancreatitis in the 180 days before screening or between screening and randomization.

• Family (first-degree relative[s]), or personal history of medullary thyroid carcinoma (MTC), or multiple endocrine neoplasia syndrome type 2 (MEN-2).

• Calcitonin ≥ 50 ng/L (pg/mL) at screening.

• Acute or chronic hepatitis; signs and symptoms of any liver disease other than metabolic dysfunction-associated steatotic liver disease, or alanine aminotransferase (ALT) > 3.0 x the upper limit of normal (ULN) during screening, or total bilirubin (TBL) > 1.8 x ULN during screening (for participants with a known diagnosis of Gilbert syndrome, direct bilirubin should be used instead of TBL).

• History of malignancy within the last 5 years before screening or between screening and randomization (except for the following treated with curative intent: non-melanoma skin cancer, breast ductal carcinoma in situ, cervical carcinoma in situ, or prostate cancer in situ).

• Participants of childbearing potential planning to become pregnant while on study or unwilling to use protocol-specified methods of contraception during treatment.