Actively Recruiting
Bariatric Surgery vs. Semaglutide vs. Tirzepatide
Led by Ali Aminian · Updated on 2026-04-02
125
Participants Needed
1
Research Sites
148 weeks
Total Duration
On this page
Sponsors
A
Ali Aminian
Lead Sponsor
E
Ethicon, Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
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
Official Title
Bariatric Surgery vs. Semaglutide vs. Tirzepatide
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Candidate for general anesthesia
- Eligible for bariatric surgery (RYGB or SG) based on ASMBS/IFSO 2022 guidelines
- Between 18 and 70 years old
- Body mass index (BMI) between 35 and 65 kg/m2
- Patients with or without type 2 diabetes mellitus (T2DM); if T2DM, stable anti-diabetic medication for at least 3 months with HbA1c 12%
- No weight loss over 20 lbs in 3 months before screening (self-reported)
- Ability and willingness to participate and provide informed consent
- Ability to understand treatment options and comply with study requirements
- Negative urine pregnancy test at randomization for women of childbearing potential
- Women of childbearing age must agree to use reliable contraception for 2 years
You will not qualify if you...
- Significant cardiac or atherosclerotic disease with planned major vascular procedures in next 12 months
- Severe uncompensated cardiopulmonary disease (ASA Class IV or V)
- New York Heart Association Class IV heart failure
- Left ventricular ejection fraction less than 25% if known
- Heart attack, unstable angina, stroke, transient ischemic attack, heart surgery, or coronary stent placement in past 6 months
- Prior bariatric surgery (except intragastric balloon removed at least 6 months before study)
- History of solid organ transplant
- Type 1 diabetes or autoimmune diabetes
- Severe kidney disease (eGFR less than 30 mL/min/1.73 m2) or dialysis
- History of deep vein thrombosis, pulmonary embolism, or venous thromboembolism
- On therapeutic anticoagulant medications
- Decompensated cirrhosis with complications
- Severe anemia (hemoglobin less than 8 g/dL)
- Use of investigational therapy
- Liver enzyme levels above 200 U/L
- Significant alcohol use (more than 2 drinks/day)
- Active cancer (except non-melanoma skin cancer)
- Life expectancy less than 3 years due to other diseases
- Major mental health or substance abuse disorders affecting surgery eligibility
- Conditions placing patient at undue risk in study
- Inability to understand risks, benefits, or comply with study
- Lack of capacity to consent
- Plans to move outside study area within 12 months
- Pregnancy, breastfeeding, or not using contraception
- Hypothalamic obesity
- Recent or continuous treatment with semaglutide or tirzepatide within 60 days
- Past use of these drugs without clinical response
- Chronic systemic steroid use
- Uncontrolled thyroid disease
- Recent or chronic pancreatitis
- History of Crohn's disease
- Allergy to semaglutide, tirzepatide, or related substances
- Personal or family history of medullary thyroid carcinoma or MEN 2
- Previous participation in this trial without proceeding after randomization
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
The Cleveland Clinic
Cleveland, Ohio, United States, 44195
Actively Recruiting
Research Team
C
Chytaine Hall
CONTACT
S
Shaghayegh Sadeghmousavi, MD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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