Bariatric Surgery Vs. Semaglutide Vs. Tirzepatide

Description

The recent introduction of the new generation of anti-obesity medications (AOMs) will change the future of obesity treatment. These highly effective medications, such as high-dose semaglutide and tirzepatide, are hormone analogues that augment the incretin function and exert multiple physiological effects by activating glucagon-like peptide-1 (GLP-1) and/or glucose-dependent insulinotropic polypeptide (GIP) distributed in various organs. These medications provide an average of 15-22% weight reduction in one-year trials, which had not been seen in the past with medical therapy. While the literature suggests that bariatric surgery is superior to these new highly effective medications, there is no head-to-head comparison between the most common bariatric operations (Roux-en-Y gastric bypass \[RYGB\] and sleeve gastrectomy \[SG\]) with semaglutide (once weekly) and tirzepatide (once weekly). The goal of this Randomized Clinical Trial (RCT) is to compare these effective therapies in patients with severe obesity to provide the best evidence to inform clinical decisions in treating patients with obesity.

Conditions

Obesity and Obesity-related Medical Conditions

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Study Overview

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Study Details

Study overview

The recent introduction of the new generation of anti-obesity medications (AOMs) will change the future of obesity treatment. These highly effective medications, such as high-dose semaglutide and tirzepatide, are hormone analogues that augment the incretin function and exert multiple physiological effects by activating glucagon-like peptide-1 (GLP-1) and/or glucose-dependent insulinotropic polypeptide (GIP) distributed in various organs. These medications provide an average of 15-22% weight reduction in one-year trials, which had not been seen in the past with medical therapy. While the literature suggests that bariatric surgery is superior to these new highly effective medications, there is no head-to-head comparison between the most common bariatric operations (Roux-en-Y gastric bypass \[RYGB\] and sleeve gastrectomy \[SG\]) with semaglutide (once weekly) and tirzepatide (once weekly). The goal of this Randomized Clinical Trial (RCT) is to compare these effective therapies in patients with severe obesity to provide the best evidence to inform clinical decisions in treating patients with obesity.

Efficacy and Safety of Bariatric Surgery, Semaglutide Once Weekly, and Tirzepatide Once Weekly in Patients with Obesity

Bariatric Surgery Vs. Semaglutide Vs. Tirzepatide

Condition
Obesity and Obesity-related Medical Conditions
Intervention / Treatment

-

Contacts and Locations

Cleveland

The Cleveland Clinic, Cleveland, Ohio, United States, 44195

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • 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
  • 5. Myocardial infarction, unstable angina, stroke, transient ischemic attack, heart surgery, coronary stent placement, venous thromboembolism in the past 6 months
  • 6. Prior bariatric surgery of any kind
  • 7. History of solid organ transplant
  • 8. Type 1 diabetes or autoimmune diabetes
  • 9. eGFR \< 30 mL/min/1.73 m2 at screening or being on dialysis
  • 10. On therapeutic dose of anticoagulants such as warfarin or direct oral anticoagulants (DOACs)
  • 11. Decompensated cirrhosis characterized by presence of ascites, hepatic encephalopathy, portal hypertension, or esophageal varices.
  • 12. Severe anemia defined as hemoglobin less than 8 g/dL
  • 13. Use of investigational therapy
  • 14. Liver transaminase level or alkaline phosphatase \>200 U/L
  • 15. Significant alcohol use (average \>2 drinks/day)
  • 16. Presence of active malignancy (except non-melanoma skin cancer)
  • 17. Life expectancy less than 3 years due to concomitant diseases
  • 18. Major mental health, psychological disorders, or substance abuse disorders that in the opinion of the investigators could disqualify the patient from bariatric surgery
  • 19. Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study
  • 20. Unable to understand the risks, benefits and compliance requirements of study
  • 21. Lack capacity to give informed consent
  • 22. Plans to move outside the primary location of study (northeast Ohio) within the next 12 months
  • 23. Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures
  • 24. Hypothalamic obesity
  • 25. Continuous treatment with semaglutide (once weekly) or tirzepatide (once weekly) \<60 days before screening
  • 26. Continuous treatment with other AOMs such as Phentermine, Topiramate, Qsymia, Contrave, etc \<60 days before screening
  • 27. Chronic use of systemic steroids
  • 28. Uncontrolled thyroid disease: thyroid stimulating hormone (TSH) \> 6.0 mIU/L or \< 0.4 mIU/L at screening
  • 29. Acute pancreatitis \< 180 days before screening
  • 30. History or presence of chronic pancreatitis
  • 31. History of Crohn's disease
  • 32. Known or suspected allergy to semaglutide, tirzepatide, excipients, or related products
  • 33. A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
  • 34. Previous participation in this trial and got randomized to one of the study groups but did not proceed.

Ages Eligible for Study

18 Years to 70 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Ali Aminian,

Ali Aminian, PRINCIPAL_INVESTIGATOR, The Cleveland Clinic

Study Record Dates

2027-12-01