Semaglutide + Tirzepatide for Obesity

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must not be taking: GLP-1RAs, Insulin, Sulfonylureas, others

Disqualifiers: Weight >137kg, Chronic GI diseases, others

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

Compensation: Varies

Number of Visits: 1

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two medications, semaglutide and tirzepatide, to evaluate their effects on obesity compared to a placebo (a substance with no active treatment). Researchers aim to understand how these medications influence the stomach's ability to empty and manage fullness over time. Suitable candidates for this trial include individuals with a BMI over 30, or over 27 if they have prediabetes or manage type 2 diabetes with diet alone, and who reside near the Mayo Clinic for the study's duration. As a Phase 4 trial, this research focuses on understanding how these FDA-approved and effective treatments can benefit more patients.

Will I have to stop taking my current medications?

You may need to stop taking some of your current medications. The trial allows certain medications like birth control, estrogen, thyroxine replacement, statins, diuretics, and some blood pressure medications, but not others that affect stomach or appetite. It's best to discuss your specific medications with the study team.

What is the safety track record for these treatments?

Research shows that semaglutide is generally well-tolerated. In one study, about 16.6% of patients stopped using it due to side effects, which can include nausea and vomiting. These side effects are common but usually mild. On the positive side, semaglutide has reduced hospital visits for heart problems and lowered the risk of major heart issues.

Studies have shown that tirzepatide can aid in weight loss. However, real-world safety data remains limited. Some people have reported side effects, but details are unclear. Both treatments have FDA approval for other uses, indicating general safety. Consulting a healthcare professional for personalized advice is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Semaglutide and Tirzepatide for obesity because these treatments offer unique approaches compared to existing options. While most weight-loss medications work by suppressing appetite or blocking fat absorption, Semaglutide and Tirzepatide are GLP-1 receptor agonists that help regulate blood sugar and insulin levels, which can lead to reduced appetite and weight loss. They are administered through a weekly subcutaneous injection, which might be more convenient than daily pills. Additionally, these treatments have shown promising results in improving metabolic health, potentially offering benefits beyond just weight reduction.

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

Research has shown that semaglutide, one of the treatments in this trial, is highly effective for weight loss. Studies found that people taking semaglutide lost an average of 14.9% of their body weight, while those on a placebo lost only 2.4%. Another study showed that patients on semaglutide lost about 15.7 kg (around 34.6 pounds) more than those not taking the medication. Tirzepatide, another treatment option in this trial, also demonstrates significant weight loss, with participants losing an average of 12.9% of their body weight over 6 months. Both treatments have shown promising results in aiding weight loss for people with obesity. ^{3 6 7 8 9}

Who Is on the Research Team?

Michael Camilleri

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with obesity. Participants must be able to receive weekly subcutaneous injections and commit to the study's duration, including follow-up tests after stopping the medication.

Inclusion Criteria

I am a man, or I am a woman using birth control and can provide negative pregnancy tests.

I am 18-75 years old with a BMI over 30, or over 27 with prediabetes or type 2 diabetes, and only on a diet treatment.

I can live within 50 miles of Mayo Clinic during the study.

Exclusion Criteria

Documented delayed gastric emptying

Participation in highly intense physical activity program

My weight is over 137kg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly subcutaneous injections of semaglutide, tirzepatide, or placebo for 24 weeks

24 weeks

Weekly visits for injections

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurements at 28 weeks

4 weeks

1 visit (in-person) at 28 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview

The study is testing two drugs: Semaglutide and Tirzepatide, against a placebo. It measures their effects on gastric emptying speed and stomach functions related to feeling full. The comparison happens over 24 weeks with additional follow-ups.

How Is the Trial Designed?

Group I: semaglutide Experimental Treatment 1 Intervention

Administered by subcutaneous injection once per week in accordance with FDA approved escalation as well as maintenance treatment

Group II: Tirzepatide Experimental Treatment 2 Interventions

Administered by subcutaneous injection once per week in accordance with FDA approved escalation as well as maintenance treatment

Group III: placebo Placebo Group 2 Interventions

Administered by subcutaneous injection once per week

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

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]

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]

Obesity is a major public health concern, with projections indicating that over 1.1 billion individuals will be affected by 2030, highlighting the urgent need for effective treatments.

GLP-1 receptor agonists, particularly semaglutide, are at the forefront of clinical development for obesity treatment, showing promise in improving metabolic health and potentially serving as a benchmark for future anti-obesity therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity. Jepsen, MM., Christensen, MB.[2022]

In a study involving 2117 participants treated with semaglutide 2.4 mg for 68 weeks, gastrointestinal adverse events (AEs) like nausea and diarrhea were more common than in the placebo group, but these AEs were mostly mild and transient, with only 4.3% of participants discontinuing treatment due to them.

Weight loss with semaglutide was significant and similar in participants with and without GI AEs, indicating that the weight loss effects of semaglutide are largely independent of these gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Wharton, S., Calanna, S., Davies, M., et al.[2022]

In a post hoc analysis of the SUSTAIN 1-3 trials involving 2432 participants with type 2 diabetes, semaglutide significantly reduced body weight (BW) by 3.7 to 6.1 kg compared to comparators, which only saw reductions of 1.0 to 1.9 kg.

The improvement in insulin resistance (IR) was primarily linked to weight loss, with 70% to 80% of the IR reduction from semaglutide 0.5 mg and 34% to 94% from semaglutide 1.0 mg being mediated by the decrease in BW.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide. Fonseca, VA., Capehorn, MS., Garg, SK., et al.[2023]

In a phase 3 trial involving 667 adults with overweight or obesity, oral semaglutide 50 mg taken daily resulted in a significant average weight loss of 15.1% compared to only 2.4% with placebo over 68 weeks, demonstrating its efficacy in weight management.

While semaglutide was effective, it was associated with a higher incidence of adverse events, particularly gastrointestinal issues, affecting 80% of participants, indicating that while it is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Knop, FK., Aroda, VR., do Vale, RD., et al.[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]

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]

Long-acting GLP-1 receptor agonists, such as liraglutide and semaglutide, are effective anti-obesity medications that can lead to significant weight loss, with semaglutide showing an average weight loss of 11.6% after one year, compared to 5.5% with liraglutide.

Both medications are generally well tolerated, with similar safety profiles, though they can cause transient gastrointestinal issues; ongoing long-term studies are needed to further evaluate their efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. Christensen, RM., Juhl, CR., Torekov, SS.[2020]

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]

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Body weight reductions of ≥5%, ≥10%, ≥15%, and ≥20% from baseline at 2 years were observed in 90.5%, 69.8%, 46.9%, and 29.6% of patients, ...

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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 ...

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In overweight or obese non-diabetic individuals, semaglutide had a remarkable and sustained weight loss effect that was well tolerated and safe.