Sequential Therapy Anti-obesitY Medication With Muscle Preservation for Weight Loss and MaintEnance: A PragmAtic Randomized CoNtrolled Trial (STAY-LEAN Trial)

1. Gender: men and women

2. Ethnicity: all ethnic groups

3. Age: ≥ 25, < 65 years

5. Obesity, BMI ≥ 30 and BMI < 45 6. An Employee, or the significant other of an employee, that is covered by the Cleveland Clinic Employee Health Plan

1. Patients with history of diabetes

2. Glomerular Filtration Rate <30 mL/min/1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration Equation, CKD-EPI)

3. Current glucocorticoid therapy, except for maintenance glucocorticoid therapy of prednisone 5 mg or equivalent

4. Currently or within the past 6 months receiving an anti-obesity medication, or any other medication used for the primary intent of weight loss

5. Any condition, unwillingness, or inability, not covered by any of the other exclusion criteria, which, in the study clinician's opinion, might jeopardize the subject's safety or compliance with the protocol

6. Mental incapacity or language barrier

7. Pregnancy or plans to become pregnant within the next 2 years

8. Personal or family history of medullary thyroid carcinoma

9. Personal or family history of Multiple Endocrine Neoplasia syndrome type 2

10. previous history of pancreatitis, history of severe liver disease (Cirrhosis), or severe disease of digestive tract

11. History of congestive heart failure

12. History of bariatric or metabolic surgery/procedure

13. Prior participation in the Endocrinology and Metabolism Institutes Integrated Weight Management Program within the past 3 months

14. Contraindication for physical activity or significant physical limitation

15. Smoking

16. Cardiovascular disease including uncontrolled hypertension, history of arrhythmias or coronary artery disease

17. History of recurrent kidney stones

18. History of glaucoma

19. History of seizure disorders

20. Uncontrolled lung disease (difficult to control Asthma or COPD)

21. Medications that affect physical performance (beta-blocker or others)

22. Uncontrolled thyroid disease

23. Patients with personal commitments that limit optimal participation

24. Concurrent use of bupropion or naltrexone or previous intolerance to any of these medic

25. Previous intolerance to use or allergy to any of the anti-obesity medications approved in this study

26. History of malabsorptive disorders or cholestasis

27. Conductive implanted devices (i.e. cardiac pacemaker, cardioverter-defibrillators)