Bariatric Surgery vs Semaglutide vs Tirzepatide for Obesity

Overseen By Chytaine Hall

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ali Aminian

Must not be taking: Anticoagulants, Steroids, AOMs, others

Disqualifiers: Cardiac disease, Transplant history, Alcohol use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

125 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on semaglutide, tirzepatide, or other anti-obesity medications within 60 days before screening. If you have type 2 diabetes, you should be on a stable dose of your anti-diabetic medication for at least 3 months before joining.

What data supports the effectiveness of the drugs semaglutide and tirzepatide for obesity?

Research shows that both semaglutide and tirzepatide are effective for weight loss, with tirzepatide often resulting in more weight loss than semaglutide. These drugs have been shown to help people lose a significant amount of weight, making them promising options for treating obesity. ^{1 2 3 4 5}

Is bariatric surgery, semaglutide, or tirzepatide safe for treating obesity?

Tirzepatide and semaglutide have been studied for safety in treating type 2 diabetes and obesity, showing mild to moderate gastrointestinal side effects like nausea and diarrhea. Bariatric surgery is a well-established procedure for obesity, but it carries surgical risks and requires careful consideration and medical advice. ^{2 5 6 7 8}

How does the treatment of obesity with tirzepatide differ from other treatments?

Tirzepatide is unique because it acts on two different receptors in the body, GLP-1 and GIP, which help control blood sugar and reduce appetite, making it potentially more effective for weight loss compared to other treatments like semaglutide or bariatric surgery. ^{1 3 7 9 10}

What is the purpose of this trial?

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.

Research Team

Ali Aminian

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for individuals with severe obesity who are looking to reduce their weight. Participants should be adults eligible for bariatric surgery and willing to take new anti-obesity medications. Specific criteria will determine eligibility, but details are not provided here.

Inclusion Criteria

I have not lost more than 20 lbs in the last 3 months.

I am willing and able to follow the study's requirements.

I am fit for general anesthesia.

Exclusion Criteria

I regularly use steroids for a long-term condition.

My thyroid condition is not under control.

I have had heart problems or procedures recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either bariatric surgery (RYGB or SG), semaglutide, or tirzepatide for the assessment of the primary endpoint

52 weeks

Extension

Participants are followed to assess the durability of effects and access to AOMs in a real-life setting

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bariatric Surgery
• Semaglutide
• Tirzepatide

Trial Overview The study compares the effectiveness of two new hormone analogue medications, Semaglutide and Tirzepatide (taken weekly), against common bariatric surgeries like RYGB and SG in reducing weight among severely obese patients.

Participant Groups

Group I: Bariatric Surgery Active Control 1 Intervention

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

Group II: Tirzepatide Active Control 1 Intervention

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

Group III: Semaglutide Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Ali Aminian

Lead Sponsor

Trials

4

Recruited

4,500+

Ethicon, Inc.

Industry Sponsor

Trials

95

Recruited

62,300+

Tim Schmid

Ethicon, Inc.

Chief Executive Officer since 2023

Undergraduate degree from the University of Western Ontario, MBA from Richmond University in the United Kingdom

Nancy Sabin

Ethicon, Inc.

Chief Medical Officer

MBA from the University of Pennsylvania’s Wharton School of Business, B.S. in Engineering from Duke University

Findings from Research

In a study involving 238 to 240 participants for tirzepatide and 240 participants for semaglutide, tirzepatide at doses of 10 mg and 15 mg significantly reduced HbA1c levels compared to semaglutide 2 mg, with reductions of -0.36% and -0.4%, respectively.

Tirzepatide also led to greater weight loss compared to semaglutide, with reductions of -3.15 kg and -5.15 kg for the 10 mg and 15 mg doses, respectively, while no significant differences were observed for the 5 mg dose of tirzepatide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. Vadher, K., Patel, H., Mody, R., et al.[2022]

Semaglutide and tirzepatide, two newly developed injectable anti-obesity medications, have shown remarkable weight-loss effects in phase III trials, significantly outperforming older anti-obesity medications that typically only reduce weight by about 5% more than placebo.

Both drugs were tested in trials involving patients with type 2 diabetes, highlighting their potential not only for weight reduction but also for improving glycemic control, making them promising options in the fight against obesity and its related health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Upcoming Weekly Tides (Semaglutide vs. Tirzepatide) against Obesity: STEP or SURPASS? Jung, HN., Jung, CH.[2022]

Tirzepatide, a dual GLP-1 and GIP receptor agonist recently approved by the FDA, shows significant effectiveness in controlling blood sugar levels in type 2 diabetes mellitus (T2DM), outperforming traditional treatments like insulin.

In addition to improving glycemic control, tirzepatide also promotes substantial weight loss, positioning it as a promising alternative to bariatric surgery for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The catcher in the gut: Tirzepatide, a dual incretin analog for the treatment of type 2 diabetes mellitus and obesity. Lempesis, IG., Liu, J., Dalamaga, M.[2022]

In a study comparing tirzepatide and semaglutide in patients with type 2 diabetes, tirzepatide demonstrated superior efficacy in reducing HbA1c levels and body weight, indicating it may be a more effective treatment option.

The trial involved a significant number of participants and showed that tirzepatide not only improved glycemic control but also had a favorable safety profile, making it a promising alternative to existing diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In type 2 diabetes, tirzepatide reduced HbA1c vs. semaglutide. Gandhi, GY.[2022]

Tirzepatide, a new GLP-1 receptor agonist, was found to be more effective for weight loss compared to other GLP-1RAs like semaglutide and liraglutide, with significant weight loss observed in over 12,300 patients in the analysis.

While all GLP-1RAs were associated with gastrointestinal side effects, tirzepatide showed better efficacy outcomes for weight loss while maintaining a similar safety profile to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials. Alkhezi, OS., Alahmed, AA., Alfayez, OM., et al.[2023]

Tirzepatide (Tir) showed superior efficacy in reducing HbA1c and body weight compared to semaglutide (Sem) in a meta-analysis of 38 studies involving 34,166 participants, making it the most effective option for treating type 2 diabetes mellitus (T2DM).

Both Tir and Sem had acceptable safety profiles, with Tir not significantly increasing gastrointestinal adverse events compared to Sem, indicating that Tir is a promising treatment for obese or overweight T2DM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation and comparison of efficacy and safety of tirzepatide and semaglutide in patients with type 2 diabetes mellitus: A Bayesian network meta-analysis. Ding, Y., Shi, Y., Guan, R., et al.[2023]

In a 72-week phase 3 trial involving 2539 adults with obesity, tirzepatide (5 mg, 10 mg, or 15 mg) resulted in significant weight loss, with mean reductions of -15.0%, -19.5%, and -20.9% respectively, compared to only -3.1% with placebo.

A high percentage of participants (85% to 91%) on tirzepatide achieved at least a 5% weight reduction, and many experienced improvements in cardiometabolic measures, although gastrointestinal side effects were the most common adverse events, mostly mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide Once Weekly for the Treatment of Obesity. Jastreboff, AM., Aronne, LJ., Ahmad, NN., et al.[2023]

Tirzepatide, a novel GLP-1 receptor agonist, has been shown to significantly reduce A1C levels and body weight in patients with type 2 diabetes compared to placebo and other active treatments.

The safety profile of tirzepatide is similar to other GLP-1 receptor agonists, with the most common side effects being mild to moderate gastrointestinal issues, and it does not increase the risk of hypoglycemia, making it a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. Kushner, P., Anderson, JE., Simon, J., et al.[2023]

Tirzepatide (15 mg) leads to a greater average weight loss of 17.8% compared to semaglutide (2.4 mg), which results in a 12.4% weight loss, making tirzepatide more effective for weight management in patients with type 2 diabetes.

In terms of cost-effectiveness, tirzepatide requires approximately $985 to achieve a 1% reduction in body weight, while semaglutide costs about $1845 for the same reduction, indicating that tirzepatide offers better value for money.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis. Azuri, J., Hammerman, A., Aboalhasan, E., et al.[2023]

Tirzepatide, a novel drug that activates both GLP-1 and GIP receptors, shows glucose-lowering and weight loss effects that are at least as effective as traditional GLP-1 receptor agonists, based on a review of studies leading to its approval.

Current evidence suggests that tirzepatide may be more effective than GLP-1 RAs for weight loss, indicating it could become the preferred treatment option for patients with or without diabetes who want to lose weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond glycemia: Comparing tirzepatide to GLP-1 analogues. Andraos, J., Muhar, H., Smith, SR.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

The Upcoming Weekly Tides (Semaglutide vs. Tirzepatide) against Obesity: STEP or SURPASS? [2022]

3. England pubmed.ncbi.nlm.nih.gov

The catcher in the gut: Tirzepatide, a dual incretin analog for the treatment of type 2 diabetes mellitus and obesity. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

In type 2 diabetes, tirzepatide reduced HbA1c vs. semaglutide. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation and comparison of efficacy and safety of tirzepatide and semaglutide in patients with type 2 diabetes mellitus: A Bayesian network meta-analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Tirzepatide Once Weekly for the Treatment of Obesity. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Beyond glycemia: Comparing tirzepatide to GLP-1 analogues. [2023]