Methods of treating overweight and obesity
The present disclosure relates to compositions, kits, uses, systems and methods for treating overweight and obesity using naltrexone plus bupropion, preferably in combination with a comprehensive web-based and/or telephone-based weight management program, and preferably in subjects at increased risk of adverse cardiovascular outcomes.
1. A method of treating overweight or obesity in a subject at increased risk of a major adverse cardiovascular event, the method comprising:
administering to an overweight or obese subject at increased risk of a major adverse cardiovascular event an amount of sustained release naltrexone or a pharmaceutically acceptable salt thereof in a range of about 4 mg to about 50 mg per day and an amount of sustained release bupropion or a pharmaceutically acceptable salt thereof in a range of about 30 mg to about 500 mg per day;
wherein said overweight or obese subject is at increased risk of a major adverse cardiovascular event if said subject has been 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 said identification;
a history of coronary revascularization including coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy;
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 said identification; and
>50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years of said identification; and
wherein said subject is treated for at least 16 weeks.
2. The method of claim 1 , wherein said subject does not have 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 said identification; and
current tobacco smoker.
3. The method of claim 1 , wherein the subject achieves a percentage of weight loss of at least 5%.
4. The method of claim 1 , wherein administering the naltrexone and bupropion does not increase said subject's risk of an adverse cardiovascular outcome.
5. The method of claim 1 , wherein said adverse cardiovascular outcome is cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
6. The method of claim 1 , wherein the subject is administered said sustained release naltrexone, or a pharmaceutically acceptable salt thereof, and said sustained release bupropion, or a pharmaceutically acceptable salt thereof, in a tablet containing 8 mg of sustained release naltrexone and 90 mg of sustained release bupropion.
7. A method of treating overweight or obesity in a subject at increased risk of a major adverse cardiovascular event, the method comprising:
administering to an overweight or obese subject at increased risk of a major adverse cardiovascular event an amount of sustained release naltrexone or a pharmaceutically acceptable salt thereof in a range of about 4 mg to about 50 mg per day and an amount of sustained release bupropion or a pharmaceutically acceptable salt thereof in a range of about 30 mg to about 500 mg per day;
wherein said overweight or obese subject is at increased risk of a major adverse cardiovascular event if said subject has been 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 said identification;
a history of coronary revascularization including coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy;
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 said identification; and
≥50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years of said identification; and
wherein the subject is administered said sustained release naltrexone, or a pharmaceutically acceptable salt thereof, and said sustained release bupropion, or a pharmaceutically acceptable salt thereof, in a tablet containing 8 mg of sustained release naltrexone and 90 mg of sustained release bupropion.
8. The method of claim 7 , wherein said subject does not have 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 said identification; and
current tobacco smoker.
9. The method of claim 7 , wherein the subject achieves a percentage of weight loss of at least 5%.
10. The method of claim 7 , wherein administering the naltrexone and bupropion does not increase said subject's risk of an adverse cardiovascular outcome.
11. The method of claim 7 , wherein said adverse cardiovascular outcome is cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
12. A method of treating a subject at increased risk of a major adverse cardiovascular event for overweight or obesity comprising:
administering to an overweight or obese subject at increased risk of a major adverse cardiovascular event an amount of sustained release naltrexone or a pharmaceutically acceptable salt thereof in a range of about 4 mg to about 50 mg per day and an amount of sustained release bupropion or a pharmaceutically acceptable salt thereof in a range of about 30 mg to about 500 mg per day;
wherein said overweight or obese subject is at increased risk of a major adverse cardiovascular event if said subject has been 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 said identification;
a history of coronary revascularization including coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy;
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 said identification; and
≥50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years of said identification; and
wherein said major adverse cardiovascular event is cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
13. The method of claim 7 , wherein said subject does not have 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 said identification; and
current tobacco smoker.
14. The method of claim 7 , wherein the subject achieves a percentage of weight loss of at least 5%.
15. The method of claim 7 , wherein administering the naltrexone and bupropion does not increase said subject's risk of an adverse cardiovascular outcome.