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Obesity and Obesity-related Medical ConditionsPhase 4NCT06803888

Bariatric Surgery vs. Semaglutide vs. Tirzepatide

A Phase 4 study testing Bariatric Surgery, Semaglutide and Tirzepatide in people with Obesity and Obesity-related Medical Conditions, run by Ali Aminian at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Bariatric Surgery, Semaglutide and Tirzepatide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
1 siteUnited States
Study dates
29 Jan 2025to 1 Dec 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%.
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  • 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.

Who cannot join

  • 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
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  • 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
  • Hypothalamic obesity
  • Continuous treatment with semaglutide (once weekly) or tirzepatide (once weekly) <60 days before screening
  • History of semaglutide (once weekly) or tirzepatide (once weekly) use in the past for obesity with lack of clinical response
  • Chronic use of systemic steroids
  • 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.
  • Acute pancreatitis < 180 days before screening
  • History or presence of chronic pancreatitis
  • History of Crohn's disease
  • Known or suspected allergy to semaglutide, tirzepatide, excipients, or related products
  • A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
  • Previous participation in this trial and got randomized to one of the study groups but did not proceed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Cleveland Clinic

    Cleveland, Ohio, 44195

Other trials in United States

About this study

Official title: Efficacy and Safety of Bariatric Surgery, Semaglutide Once Weekly, and Tirzepatide Once Weekly in Patients With Obesity

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.

Read the detailed description

This is a randomized, non-blinded, controlled efficacy/safety study with 3 parallel groups who will either receive bariatric surgery (RYGB or SG), semaglutide, or tirzepatide. The study has 2 phases: the first 12 months for the assessment of the primary endpoint ( mean percentage weight loss) and the second 12 months as the extension phase of the study to mimic the real-life setting. Findings at the end of each phase will be separately reported. A randomized trial of adult patients with a BMI of 35-65 kg/m2 who seek treatment for obesity at Cleveland Clinic will be performed. Patients who meet the ASMBS/IFSO 2022 guidelines for bariatric surgery will be invited for possible enrollment. Interested and eligible patients will be randomized to receive their already chosen bariatric surgery (RYGB or SG), tirzepatide. or semaglutide in 2:2:1 ratio. The study targets approximately 140 participants who initiate their assigned treatment for the primary efficacy analysis.

The study is not intended to compare RYGB vs SG head-to-head. RYGB and SG constitute one group as a bariatric surgery group. The assignment of RYGB or SG is not based on a randomized design. Each patient and surgical team will make a shared decision about the most appropriate surgical procedure. The study is also not intended to compare semaglutide vs tirzepatide head-to-head.

In the second or extension phase of the study, participants are followed from month 12 to month 24, regardless of the treatment that they receive. In this phase, the study medications (semaglutide and tirzepatide) will not be provided by the study. The goal of this phase is to provide valuable insights into A) access to AOMs and the durability of effects in the real-life setting, B) cross-over from AOMs to bariatric surgery, and C) adjuvant pharmacotherapy after bariatric surgery.

Being tested
Bariatric Surgery, Semaglutide, Tirzepatide
Keywords
Bariatric Surgery, Tirzepatide, Semaglutide, Obesity, GLP-1 Receptor Agonist, Mounjaro, Wegovy, Zepbound, Ozempic, Sleeve Gastrectomy, Roux-en-Y gastric bypass
Medical subject headings
Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bariatric SurgeryProcedure or surgery

    Also called Metabolic Surgery, Roux-en-Y Gastric Bypass (RYGB), Sleeve Gastrectomy (SG)

    Patients receive either RYGB or SG. The surgical risk, the differential impact of each procedure on body weight and other obesity-related diseases, presence of other medical and mental problems, patient's behavioral factors (e.g., postoperative compliance, active smoking), medications, and goals will be considered when the patient and local medical team make a shared decision about the most appropriate surgical procedure.

  • SemaglutideDrug

    Also called Ozempic, Wegovy

    Semaglutide will be initiated at a dose of 0.25 mg once weekly and will be increased during the dose-escalation period to reach a maintenance dose of up to 2.4 mg once weekly by week 16. If patients do not tolerate a dose during dose escalation, we will consider delaying dose escalation until next visit (for 4 weeks). Dosing for Semaglutide is the FDA-approved dosing schedule.

    The maintenance dose is 2.4 mg injected subcutaneously once-weekly. The protocol allows for dose reductions in case a participant does not tolerate the recommended target dose of 2.4 mg and may stay at the lower maintenance dose level (e.g., 1.7 mg once weekly), if needed.

  • TirzepatideDrug

    Also called Mounjaro, Zepbound

    Tirzepatide will be initiated at a dose of 2.5 mg once weekly and will be increased by 2.5 mg every four weeks during the dose-escalation period to reach a maintenance dose of up to 15 mg once weekly by week 20. If patients do not tolerate a dose during dose escalation, we will consider delaying dose escalation until next visit (for 4 weeks). Dosing for Tirzepatide is the FDA-approved dosing schedule.

    The maintenance dose is 15 mg injected subcutaneously once-weekly. The protocol allows for dose reductions in case a participant does not tolerate the recommended target dose of 15 mg and may stay at the lower maintenance dose level (e.g., 10 mg once weekly), if needed.

Study groups in NCT06803888
Study groupRoleWhat they receive
Bariatric SurgeryActive comparatorRoux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG)
Receives: Procedure: Bariatric Surgery
SemaglutideActive comparatorSemaglutide, which is an incretin-based medication that has been approved for the treatment of obesity, will be used for this arm.
Receives: Drug: Semaglutide
TirzepatideActive comparatorTirzepatide, which is an incretin-based medication that has been approved for the treatment of obesity, will be used for this arm.
Receives: Drug: Tirzepatide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean percentage total body weight loss at Week 52

    The mean percentage weight loss at 52 weeks after treatment initiation for the following 2 comparisons:

    • Bariatric surgery (RYGB and SG) vs tirzepatide
    • Bariatric surgery (RYGB and SG) vs semaglutide

    Measured: Baseline to Week 52 after treatment initiation

Secondary outcomes (18)

  1. Percentage of Participants Achieving Weight Loss Milestones (Body weight related end points)

    Percentage of participants achieving ≥5%, ≥10%, ≥15%, ≥20%, ≥25%, ≥30%, and ≥35% weight loss from baseline

    Measured: Baseline to Week 52

  2. Absolute Change in Weight (Body weight related end points)

    Mean absolute change in weight measured in kilograms from baseline to 52 weeks

    Measured: Baseline to Week 52

  3. Absolute Change in BMI (Body weight related end points)

    Absolute change in BMI measured in kg/m^2 from baseline to 52 weeks

    Measured: Baseline to Week 52

  4. Excess Weight Loss Percentage (Body weight related end points)

    Percentage of excess weight loss, calculated by dividing the difference between initial BMI and final BMI by the difference between initial BMI and a target BMI of 25

    Measured: Baseline to Week 52

  5. Change in Waist Circumference (Body weight related end points)

    Change in waist circumferential measurement above the level of the iliac crests measured in centimeters from baseline to 52 weeks

    Measured: Baseline to Week 52

  6. Change in waist-to-height ratio (WHtR)

    Change in waist-to-height ratio from baseline to Week 52

    Measured: Baseline to Week 52

  7. Systolic blood pressure trends

    Mean and change in systolic blood pressure measured in mmHg

    Measured: Baseline to Week 52

  8. Mean and change from baseline in lipid panel

    Mean and change from baseline in total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides measured in mg/dL

    Measured: Baseline to Week 52

  9. Changes in glucose homeostasis markers in T2DM patients

    Mean and change from baseline in blood glucose (measured in mg/dL) and HbA1c (as a percentage) in patients with T2DM

    Measured: Baseline to Week 52

  10. Percentage of patients with T2DM meeting predefined HbA1c targets

    Percentage of patients meeting different HbA1c targets, for example:

    • HbA1c <6.5% (without diabetes medications)
    • HbA1c <7% (irrespective of taking diabetes medications or not)

    Measured: Baseline to Week 52

  11. Changes in inflammatory marker, CRP

    Mean and change from baseline in C-Reactive Protein (CRP) measured in mg/L

    Measured: Baseline to Week 52

  12. Changes in Lipoprotein(a)

    Mean and change from baseline in Lipoprotein(a) measured in mg/dL

    Measured: Baseline to Week 52

  13. Change in cardiovascular and diabetes medications

    Change in the number of cardiovascular and diabetes medications prescribed

    Measured: Baseline to Week 52

  14. Change from baseline in quality of life metrics

    Change from baseline in score of The 36-Item Short Form Health Survey (SF-36) (physical and mental components). Each item is given a score ranging from 0-100. Lower scores indicating poor outcomes. Final score is an average of all the items that were answered. Unanswered questions are not included in the final average. Research coordinator completes the survey with the patient.

    Measured: Baseline to Weeks 52 and 104

  15. Change in body composition (via Seca mBCA 554 Bioimpedance Analysis)

    Change in body composition (% fat mass and % fat-free mass) as measured by Seca mBCA 554 Bioimpedance Analysis to assess whether that weight loss is primarily caused by reduction in fat mass or not.

    Measured: Baseline to Weeks 52

  16. Mean change in liver fat content (via MRI-PDFF)

    Mean change from baseline in liver fat content as assessed by MRI-PDFF measured as a percentage

    Measured: Baseline to Weeks 52

  17. Percentage of Participants Achieving ≥5%, ≥30%, ≥50% Absolute Reduction in Liver Fat Content (via MRI-PDFF)

    Percentage of participants achieving at least 5%, 30%, or 50% relative reduction in liver fat content from baseline

    Measured: Baseline to Weeks 52

  18. Percentage of Participants Achieving MRI-PDFF Normalization (via MRI-PDFF)

    Percentage of participants achieving MRI-PDFF normalization, defined as a liver fat content of <5%, at week 52

    Measured: Baseline to Weeks 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2025
  2. Study start29 Jan 2025
  3. Primary completion1 Jul 2027 (estimated)
  4. Study completion1 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a randomized non-blinded controlled efficacy/safety study with 3 parallel groups who will either receive bariatric surgery (RYGB or SG), semaglutide, or tirzepatide. The study has 2 phases: the first 12 months for the assessment of the primary endpoint, and the second 12 months as the extension phase of the study to mimic the real-life setting. Findings at the end of each phase will be separately reported.
Masking
None (open label)
Enrolment
140 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06803888
Sponsor's protocol ID
24-915
Status last verified
Aug 2026
First submitted
14 Jan 2025
Last updated
3 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Bariatric Surgery, Semaglutide and Tirzepatide in people with Obesity and Obesity-related Medical Conditions, run by Ali Aminian at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean percentage total body weight loss at Week 52 (time frame: Baseline to Week 52 after treatment initiation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06803888.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.

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