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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare three different obesity treatments: bariatric surgery, semaglutide (a medication), and tirzepatide (a medication). Researchers seek to determine which method is most effective for individuals with severe obesity. Participants should have a body mass index (BMI) between 35 and 65 and be eligible for general anesthesia. Those considering bariatric surgery or exploring new medications for weight loss might find this trial suitable. As a Phase 4 trial, the treatments have already received FDA approval and demonstrated effectiveness, providing an opportunity to observe their benefits in a broader patient population.

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 is the safety track record for these treatments?

Research has shown that semaglutide is generally safe and effective for weight loss in people with obesity. One study found it helped people lose weight over time and was considered safe. However, some participants discontinued use due to side effects, with about 16.6% stopping treatment. This indicates that while semaglutide is effective, it may not be suitable for everyone without side effects.

For tirzepatide, studies indicate it is also effective for weight loss, but real-world safety information remains limited. Some reports mention side effects, but the treatment generally aids in significant weight loss. This suggests that while tirzepatide appears promising, more information may be needed to fully understand its safety.

Both medications have FDA approval for treating obesity, indicating they are safe enough for use. However, it is important to consider the benefits and risks and discuss them with a doctor. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for obesity because they each offer unique advantages. Bariatric surgery, such as Roux-en-Y Gastric Bypass and Sleeve Gastrectomy, provides a surgical solution that physically alters the digestive system to promote weight loss. On the other hand, Semaglutide and Tirzepatide are incretin-based medications. Semaglutide mimics a hormone involved in appetite regulation, potentially leading to significant weight loss without surgery. Tirzepatide not only mimics this hormone but also targets additional pathways, potentially offering even greater effectiveness. This variety in approaches gives patients and doctors more options tailored to individual needs and responses.

What evidence suggests that this trial's treatments could be effective for obesity?

This trial will compare the effectiveness of bariatric surgery, semaglutide, and tirzepatide for obesity. Studies have shown that weight-loss surgery, such as gastric bypass and sleeve gastrectomy, often leads to long-term results, with some patients maintaining a weight loss of more than 20% even after 10 years. Participants in this trial may receive bariatric surgery as one treatment option. Another arm of the trial will involve semaglutide, which has helped people lose about 15% of their weight in a year, with some losing even more. Tirzepatide, which participants in another arm of this trial may receive, has demonstrated impressive results, with participants losing up to 20% of their body weight in studies. Each treatment works effectively but offers different benefits due to their distinct mechanisms. ^{6 7 8 9 10}

Who Is on the Research Team?

Ali Aminian

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 (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]

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, 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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40709782/

Evaluating the Effectiveness and Long-term Outcomes of ... Results: RYGB was associated with more significant long-term weight loss and superior T2DM remission rates. SG had a lower risk of nutritional ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666776224000024

Long-term effect of sleeve gastrectomy vs Roux-en-Y ... Total weight loss at 5 years was 22.5% [95% CI, 20.7%–24.3%] after sleeve gastrectomy and 26.0% [95% CI, 24.3%–27.8%] after Roux-en-Y gastric bypass (difference ...

3. asmbs.org asmbs.org/news_releases/new-study-shows-long-term-effectiveness-of-gastric-bypass-in-treating-type-2-diabetes-and-obesity/

New Study Shows Long-term Effectiveness of Gastric ... Peak weight loss of 31.8% was achieved after 18 months and stabilized at 23% after 10 years and up to the 20-year mark. The overall 15-year ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2814336

Comparison of Sleeve Gastrectomy vs Roux-en-Y Gastric ... Roux-en-Y gastric bypass has a long track record, and available observational data demonstrate sustained weight loss and improvement in obesity- ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1700459

Weight and Metabolic Outcomes 12 Years after Gastric ... Furthermore, at 10 years, 72% of the patients who had undergone Roux-en-Y gastric bypass had maintained at least a 20% weight loss from baseline ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa2307563

Semaglutide and Cardiovascular Outcomes in Obesity ... Adverse events leading to permanent discontinuation of the trial product occurred in 1461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39396098/

Semaglutide effects on safety and cardiovascular ... Conclusion: The use of semaglutide reduced 76% in hospitalization due to HF, 17% deaths due to cardiovascular causes, 21% deaths due to any ...

8. nature.com nature.com/articles/s41591-024-02996-7

Long-term weight loss effects of semaglutide in obesity ... In SELECT, semaglutide was associated with a 20% reduction in major adverse CV events (hazard ratio 0.80, 95% confidence interval (CI) 0.72 to ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0002914924003199

A Systematic Review and Meta-Analysis of Randomized ... Our results suggest that semaglutide is beneficial for promoting sustained weight loss in adults with overweight/obesity and without diabetes.

10. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.15386

Efficacy and safety of semaglutide 2.4 mg for weight loss in ... In overweight or obese non-diabetic individuals, semaglutide had a remarkable and sustained weight loss effect that was well tolerated and safe.