Bariatric Surgery vs. Semaglutide vs. Tirzepatide

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

Interventions

PROCEDURE

Bariatric Surgery

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.

DRUG

Semaglutide

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.

DRUG

Tirzepatide

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.

Sponsors & Collaborators

• Ethicon, Inc.

  collaborator INDUSTRY

• Ali Aminian

  lead OTHER

Principal Investigators

• Ali Aminian · The Cleveland Clinic

• Ali Aminian, MD · The Cleveland Clinic

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-01-29

Primary Completion

2027-07-01

Completion

2027-12-01

FDA Drug

Yes

Countries

• United States

Study Locations