Entry into the study would require that the patient:

1. Is a candidate for general anesthesia

2. Is eligible for bariatric surgery (RYGB or SG) based on ASMBS/IFSO 2022 guidelines

3. Is ≥18 and ≤70 years old (both inclusive)

4. has a BMI ≥35 and ≤65 kg/m2 (both inclusive)

5. Patients with and without T2DM are eligible for the study. Patients with T2DM should have been on a stable dose of anti-diabetic medication (including insulin but not semaglutide or tirzepatide) for at least 3 months prior to entry, with HbA1c ≤12%.

6. No weight loss > 20 lbs. in 3 months before screening (self-reported)

7. Has the ability and willingness to participate in the study, provide informed consent, and agree to any of the arms involved in the study.

8. Is able to understand the options and to comply with the requirements of each arm.

9. Has a negative urine pregnancy test at randomization visit for women of childbearing potential.

10. Women of childbearing age must agree to use reliable method of contraception for 2 years.

1. Significant cardiac or atherosclerotic disease (planned to undergo cardiac, coronary, carotid, or peripheral artery revascularization procedures in the next 12 months)

2. Severe uncompensated cardiopulmonary disease leading to American Society of Anesthesiologists Class IV or V

3. Classified as New York Heart Association Class IV

4. Left ventricular ejection fraction <25% at the time of screening (if already known)

5. Myocardial infarction, unstable angina, stroke, transient ischemic attack, heart surgery, coronary stent placement in the past 6 months

6. Prior bariatric surgery of any kind

• Intragastric balloon that has been removed at least 6 months prior to the first study visit is allowed.

7. History of solid organ transplant

8. Type 1 diabetes or autoimmune diabetes

9. eGFR < 30 mL/min/1.73 m2 or being on dialysis

10. History of deep vein thrombosis, pulmonary embolism, or venous thromboembolism

11. On therapeutic dose of anticoagulants such as warfarin or direct oral anticoagulants (DOACs)

12. Decompensated cirrhosis characterized by presence of ascites, hepatic encephalopathy, portal hypertension, or esophageal varices.

13. History of severe anemia defined as hemoglobin less than 8 g/dL

14. Use of investigational therapy

15. Liver transaminase level or alkaline phosphatase >200 U/L

16. Significant alcohol use (average >2 drinks/day)

17. Presence of active malignancy (except non-melanoma skin cancer)

18. Life expectancy less than 3 years due to concomitant diseases

19. Major mental health, psychological disorders, or substance abuse disorders that in the opinion of the investigators could disqualify the patient from bariatric surgery

20. Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study

21. Unable to understand the risks, benefits and compliance requirements of study

22. Lack capacity to give informed consent

23. Plans to move outside the primary location of study (northeast Ohio) within the next 12 months

24. Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures

25. Hypothalamic obesity

26. Continuous treatment with semaglutide (once weekly) or tirzepatide (once weekly) <60 days before screening

27. History of semaglutide (once weekly) or tirzepatide (once weekly) use in the past for obesity with lack of clinical response

28. Chronic use of systemic steroids

29. Uncontrolled thyroid disease: thyroid stimulating hormone (TSH) > 6.0 mIU/L or < 0.1 mIU/L

• Note: Patients receiving treatment for hypothyroidism can be included if their thyroid hormone replacement dose has been stable for at least 3 months.

30. Acute pancreatitis < 180 days before screening

31. History or presence of chronic pancreatitis

32. History of Crohn's disease

33. Known or suspected allergy to semaglutide, tirzepatide, excipients, or related products

34. A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)

35. Previous participation in this trial and got randomized to one of the study groups but did not proceed.