Maridebart Cafraglutide for Heart Disease and Obesity

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.