Bariatric Surgery vs. Semaglutide vs. Tirzepatide
Running, not enrolling · Phase 4
Conditions studied: Obesity and Obesity-related Medical Conditions
In brief
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.
Key facts
- Study ID
- NCT06803888
- Run by
- Ali Aminian
- People needed
- 125
- Starts
- 2025-01-29
- Expected to finish
- 2027-12-01
- Last updated by the study team
- 2026-05-18
Who can join
Age: 18 and older, up to 70. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- Entry into the study would require that the patient:
- Is a candidate for general anesthesia
- Is eligible for bariatric surgery (RYGB or SG) based on ASMBS/IFSO 2022 guidelines
- Is ≥18 and ≤70 years old (both inclusive)
- has a BMI ≥35 and ≤65 kg/m2 (both inclusive)
- 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%.
- No weight loss > 20 lbs. in 3 months before screening (self-reported)
- Has the ability and willingness to participate in the study, provide informed consent, and agree to any of the arms involved in the study.
- Is able to understand the options and to comply with the requirements of each arm.
- Has a negative urine pregnancy test at randomization visit for women of childbearing potential.
- Women of childbearing age must agree to use reliable method of contraception for 2 years.
You may not qualify if…
- Significant cardiac or atherosclerotic disease (planned to undergo cardiac, coronary, carotid, or peripheral artery revascularization procedures in the next 12 months)
- Severe uncompensated cardiopulmonary disease leading to American Society of Anesthesiologists Class IV or V
- Classified as New York Heart Association Class IV
- Left ventricular ejection fraction <25% at the time of screening (if already known)
- Myocardial infarction, unstable angina, stroke, transient ischemic attack, heart surgery, coronary stent placement in the past 6 months
- Prior bariatric surgery of any kind
- Intragastric balloon that has been removed at least 6 months prior to the first study visit is allowed.
- History of solid organ transplant
- Type 1 diabetes or autoimmune diabetes
- eGFR < 30 mL/min/1.73 m2 or being on dialysis
- History of deep vein thrombosis, pulmonary embolism, or venous thromboembolism
- On therapeutic dose of anticoagulants such as warfarin or direct oral anticoagulants (DOACs)
- Decompensated cirrhosis characterized by presence of ascites, hepatic encephalopathy, portal hypertension, or esophageal varices.
- History of severe anemia defined as hemoglobin less than 8 g/dL
- Use of investigational therapy
- Liver transaminase level or alkaline phosphatase >200 U/L
- Significant alcohol use (average >2 drinks/day)
- Presence of active malignancy (except non-melanoma skin cancer)
- Life expectancy less than 3 years due to concomitant diseases
- Major mental health, psychological disorders, or substance abuse disorders that in the opinion of the investigators could disqualify the patient from bariatric surgery
- Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study
- Unable to understand the risks, benefits and compliance requirements of study
- Lack capacity to give informed consent
- Plans to move outside the primary location of study (northeast Ohio) within the next 12 months
- Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures
Where it is running
- The Cleveland Clinic — Cleveland, Ohio, United States
Full record on ClinicalTrials.gov
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