A composition comprising sustained release naltrexone, or a pharmaceutically acceptable salt thereof, and sustained release bupropion, or a pharmaceutically acceptable salt thereof for use in treating a subject for overweight or obesity, wherein said subject has an increased risk of an adverse cardiovascular outcome, wherein said overweight or obese subject has an increased risk of an adverse cardiovascular outcome if said subject: a.) is diagnosed as having cardiovascular disease with at least one risk factor selected from the group consisting of: a history of documented myocardial infarction >3 months prior to identifying the subject; a history of coronary revascularization including coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy; a history of carotid or peripheral revascularization, including carotid endarterectomy, lower extremity atherosclerotic disease atherectomy, repair of abdominal aorta aneurysm, femoral or popliteal bypass; angina with ischemic changes, ECG changes on a graded exercise test, or positive cardiac imaging study; ankle brachial index <0.9 assessed by simple palpation within prior 2 years of identifying the subject; and ≥50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years of identifying the subject; and/or b.) is diagnosed as having Type 2 diabetes mellitus with at least 2 risk factors selected from the group consisting of: hypertension controlled with or without pharmacotherapy at <145/95 mm Hg; dyslipidemia requiring pharmacotherapy; documented low HDL cholesterol, <50 mg/dL in women or <40 mg/dL in men, within prior 12 months of identifying the subject; and current tobacco smoker. a.) is diagnosed as having cardiovascular disease with at least one risk factor selected from the group consisting of: a history of documented myocardial infarction >3 months prior to identifying the subject; a history of coronary revascularization including coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy; a history of carotid or peripheral revascularization, including carotid endarterectomy, lower extremity atherosclerotic disease atherectomy, repair of abdominal aorta aneurysm, femoral or popliteal bypass; angina with ischemic changes, ECG changes on a graded exercise test, or positive cardiac imaging study; ankle brachial index <0.9 assessed by simple palpation within prior 2 years of identifying the subject; and ≥50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years of identifying the subject; and/or a history of documented myocardial infarction >3 months prior to identifying the subject; a history of coronary revascularization including coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy; a history of carotid or peripheral revascularization, including carotid endarterectomy, lower extremity atherosclerotic disease atherectomy, repair of abdominal aorta aneurysm, femoral or popliteal bypass; angina with ischemic changes, ECG changes on a graded exercise test, or positive cardiac imaging study; ankle brachial index <0.9 assessed by simple palpation within prior 2 years of identifying the subject; and ≥50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years of identifying the subject; and/or b.) is diagnosed as having Type 2 diabetes mellitus with at least 2 risk factors selected from the group consisting of: hypertension controlled with or without pharmacotherapy at <145/95 mm Hg; dyslipidemia requiring pharmacotherapy; documented low HDL cholesterol, <50 mg/dL in women or <40 mg/dL in men, within prior 12 months of identifying the subject; and current tobacco smoker. hypertension controlled with or without pharmacotherapy at <145/95 mm Hg; dyslipidemia requiring pharmacotherapy; documented low HDL cholesterol, <50 mg/dL in women or <40 mg/dL in men, within prior 12 months of identifying the subject; and current tobacco smoker.