Bariatric Surgery vs. Semaglutide vs. Tirzepatide

NCT06803888 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 24-915
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

Brief 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 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

Keywords

Bariatric Surgery; Tirzepatide; Semaglutide; Obesity; GLP-1 Receptor Agonist; Mounjaro; Wegovy; Zepbound; Ozempic; Sleeve Gastrectomy; Roux-en-Y gastric bypass

Outcome Measures

Primary Outcomes (1)

• The mean percentage weight loss

  The mean percentage weight loss at 52 weeks for the following 2 comparisons: * Bariatric surgery (RYGB and SG) vs tirzepatide * Bariatric surgery (RYGB and SG) vs semaglutide

  First 52 weeks of the study

Secondary Outcomes (17)

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

  First 52 weeks of the study

• Absolute Change in Weight (Body weight related end points)

  First 52 weeks of the study

• Absolute Change in BMI (Body weight related end points)

  First 52 weeks of the study

• Excess Weight Loss Percentage (Body weight related end points)

  First 52 weeks of the study

• Change in Waist Circumference (Body weight related end points)

  First 52 weeks of the study

Other Outcomes (8)

• Cardiac ejection fraction (via cardiac MRI)

  First 52 weeks of the study

• Left ventricular mass (via cardiac MRI)

  First 52 weeks of the study

• Pericardial fat fraction (via cardiac MRI)

  First 52 weeks of the study

Study Arms (3)

Bariatric Surgery

ACTIVE COMPARATOR

Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG)

Procedure: Bariatric Surgery

Semaglutide

ACTIVE COMPARATOR

Semaglutide, which is an incretin-based medication that has been approved for the treatment of obesity, will be used for this arm.

Drug: Semaglutide

Tirzepatide

ACTIVE COMPARATOR

Tirzepatide, which is an incretin-based medication that has been approved for the treatment of obesity, will be used for this arm.

Drug: Tirzepatide

Interventions

Bariatric Surgery PROCEDURE

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.

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

Bariatric Surgery

Semaglutide DRUG

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.

Also known as: Ozempic, Wegovy

Semaglutide

Tirzepatide DRUG

Tirzepatide will be initiated at a dose of 2.5 mg once weekly and will be increased by 2.5 mg every week 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.

Also known as: Mounjaro, Zepbound

Tirzepatide

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Sponsors & Collaborators

• Ali Aminian: lead
• Ethicon, Inc.: collaborator

Study Sites (1)

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

MeSH Terms

Conditions

Obesity

Interventions

Bariatric Surgery; Gastric Bypass; semaglutide; Tirzepatide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bariatrics; Obesity Management; Therapeutics; Surgical Procedures, Operative; Gastroenterostomy; Anastomosis, Surgical; Digestive System Surgical Procedures; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Ali Aminian

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

• Ali Aminian, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chytaine Hall

CONTACT

(216) 445-3983; hallc1@ccf.org

Shaghayegh Sadeghmousavi, MD

CONTACT

(216) 445-0045; SADEGHS3@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the Bariatric and Metabolic Institute

Model Details: 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.

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: January 31, 2025
• Study Start: January 29, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 2, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)