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Trial · Interventional

Active, not recruitingPhase 4Registry data

Bariatric Surgery vs. Semaglutide vs. Tirzepatide

Overview

Status
Active, not recruiting
Phase
Phase 4
Enrollment
140 participants (estimated)
Sponsor
Ali Aminian · Other
Design
Randomized · Open label (no masking)
Countries
1 country

United States

Start
29 Jan 2025
Primary completion
1 Jul 2027 (estimated)
Completion
1 Dec 2027 (estimated)
First posted
31 Jan 2025
Last update posted
3 Sept 2026
Conditions
Obesity and Obesity-related Medical Conditions

Timeline

1 trial · 1 ongoing

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2025202620272028
  1. Ph 4

    Bariatric Surgery vs. Semaglutide vs. Tirzepatide

    NCT06803888

    29 Jan 2025 to est. 1 Dec 2027

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • Bariatric SurgeryProcedure
  • SemaglutideDrug
  • TirzepatideDrug

Arms3

  • Active comparator

    Bariatric Surgery

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

  • Active comparator

    Semaglutide

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

  • Active comparator

    Tirzepatide

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

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Mean percentage total body weight loss at Week 52

    Time frame · Baseline to Week 52 after treatment initiation

    Registry description

    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

Secondary outcomes(18)
  1. Percentage of Participants Achieving Weight Loss Milestones (Body weight related end points)

    Time frame · Baseline to Week 52

    Registry description

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

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

    Time frame · Baseline to Week 52

    Registry description

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

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

    Time frame · Baseline to Week 52

    Registry description

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

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

    Time frame · Baseline to Week 52

    Registry description

    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

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

    Time frame · Baseline to Week 52

    Registry description

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

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

    Time frame · Baseline to Week 52

    Registry description

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

  7. Systolic blood pressure trends

    Time frame · Baseline to Week 52

    Registry description

    Mean and change in systolic blood pressure measured in mmHg

  8. Mean and change from baseline in lipid panel

    Time frame · Baseline to Week 52

    Registry description

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

  9. Changes in glucose homeostasis markers in T2DM patients

    Time frame · Baseline to Week 52

    Registry description

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

  10. Percentage of patients with T2DM meeting predefined HbA1c targets

    Time frame · Baseline to Week 52

    Registry description

    Percentage of patients meeting different HbA1c targets, for example: * HbA1c \<6.5% (without diabetes medications) * HbA1c \<7% (irrespective of taking diabetes medications or not)

  11. Changes in inflammatory marker, CRP

    Time frame · Baseline to Week 52

    Registry description

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

  12. Changes in Lipoprotein(a)

    Time frame · Baseline to Week 52

    Registry description

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

  13. Change in cardiovascular and diabetes medications

    Time frame · Baseline to Week 52

    Registry description

    Change in the number of cardiovascular and diabetes medications prescribed

  14. Change from baseline in quality of life metrics

    Time frame · Baseline to Weeks 52 and 104

    Registry description

    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.

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

    Time frame · Baseline to Weeks 52

    Registry description

    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.

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

    Time frame · Baseline to Weeks 52

    Registry description

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

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

    Time frame · Baseline to Weeks 52

    Registry description

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

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

    Time frame · Baseline to Weeks 52

    Registry description

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

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

A trial that is still running, or that stopped early, may post results later.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 70 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: Entry into the study would require that the patient: 1. Is a candidate for general anesthesia 2. Is eligible for bariatric surgery (RYGB or SG) based on ASMBS/IFSO 2022 guidelines 3. Is ≥18 and ≤70 years old (both inclusive) 4. has a BMI ≥35 and ≤65 kg/m2 (both inclusive) 5. 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%. 6. No weight loss \> 20 lbs. in 3 months before screening (self-reported) 7. Has the ability and willingness to participate in the study, provide informed consent, and agree to any of the arms involved in the study. 8. Is able to understand the options and to comply with the requirements of each arm. 9. Has a negative urine pregnancy test at randomization visit for women of childbearing potential. 10. Women of childbearing age must agree to use reliable method of contraception for 2 years. Exclusion Criteria: 1. Significant cardiac or atherosclerotic disease (planned to undergo cardiac, coronary, carotid, or peripheral artery revascularization procedures in the next 12 months) 2. Severe uncompensated cardiopulmonary disease leading to American Society of Anesthesiologists Class IV or V 3. Classified as New York Heart Association Class IV 4. Left ventricular ejection fraction \<25% at the time of screening (if already known) 5. Myocardial infarction, unstable angina, stroke, transient ischemic attack, heart surgery, coronary stent placement in the past 6 months 6. Prior bariatric surgery of any kind • Intragastric balloon that has been removed at least 6 months prior to the first study visit is allowed. 7. History of solid organ transplant 8. Type 1 diabetes or autoimmune diabetes 9. eGFR \< 30 mL/min/1.73 m2 or being on dialysis 10. History of deep vein thrombosis, pulmonary embolism, or venous thromboembolism 11. On therapeutic dose of anticoagulants such as warfarin or direct oral anticoagulants (DOACs) 12. Decompensated cirrhosis characterized by presence of ascites, hepatic encephalopathy, portal hypertension, or esophageal varices. 13. History of severe anemia defined as hemoglobin less than 8 g/dL 14. Use of investigational therapy 15. Liver transaminase level or alkaline phosphatase \>200 U/L 16. Significant alcohol use (average \>2 drinks/day) 17. Presence of active malignancy (except non-melanoma skin cancer) 18. Life expectancy less than 3 years due to concomitant diseases 19. Major mental health, psychological disorders, or substance abuse disorders that in the opinion of the investigators could disqualify the patient from bariatric surgery 20. Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study 21. Unable to understand the risks, benefits and compliance requirements of study 22. Lack capacity to give informed consent 23. Plans to move outside the primary location of study (northeast Ohio) within the next 12 months 24. Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures 25. Hypothalamic obesity 26. Continuous treatment with semaglutide (once weekly) or tirzepatide (once weekly) \<60 days before screening 27. History of semaglutide (once weekly) or tirzepatide (once weekly) use in the past for obesity with lack of clinical response 28. Chronic use of systemic steroids 29. 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. 30. Acute pancreatitis \< 180 days before screening 31. History or presence of chronic pancreatitis 32. History of Crohn's disease 33. Known or suspected allergy to semaglutide, tirzepatide, excipients, or related products 34. A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 35. Previous participation in this trial and got randomized to one of the study groups but did not proceed.

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