Bariatric Surgery + Semaglutide for Obesity

(PRESSURE Trial)

Recruiting at 1 trial location

Overseen By Jaime Moore, MD MPH

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Colorado, Denver

Must not be taking: Glucocorticoids, Insulin, Metformin, others

Disqualifiers: Diabetes, Hypertension, Heart disease, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how young people respond to bariatric surgery, a type of weight-loss surgery. It seeks to understand why some individuals don't lose as much weight as expected and whether semaglutide, a medication used to treat obesity, can help in these cases. Participants will either be observed or receive semaglutide in addition to their usual postoperative care. Those who underwent vertical sleeve gastrectomy and haven't lost much weight 1 to 2 years afterward may be suitable candidates. As a Phase 1 trial, this research focuses on understanding how semaglutide works in people, offering participants a chance to contribute to early-stage treatment insights.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. You cannot use oral glucocorticoids, insulin, metformin, insulin secretagogues, or anti-obesity medications close to the start of the study. If you are on medications for hypertension, dyslipidemia, depression, or anxiety, they should not have been changed within 4 weeks prior to enrollment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study tested semaglutide for weight loss in adults over 68 weeks, comparing it to a placebo (a substance with no active ingredients). The results showed that semaglutide was generally safe and aided weight loss. Most participants tolerated it well, though some experienced side effects like nausea or vomiting, which were usually mild and resolved on their own.

Semaglutide has also been studied in individuals who underwent weight-loss surgery. Research has shown it can aid weight loss after surgery, although it does not enhance weight loss before surgery. While semaglutide is effective, it does not replace the benefits of surgery but serves as additional support for those who need it.

Overall, semaglutide is considered safe for individuals who have had weight-loss surgery. The ongoing study aims to further explore its effects on younger individuals who haven't lost as much weight as expected after surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using semaglutide in conjunction with bariatric surgery for obesity because it offers a unique approach to enhancing weight loss outcomes. Unlike standard postoperative care, which typically involves lifestyle changes and monitoring, semaglutide is a medication that mimics a hormone involved in appetite regulation, leading to reduced hunger and increased feelings of fullness. This medication is administered via a weekly injection, allowing for a gradual increase in dose to maximize patient tolerance and effectiveness. By targeting the hormonal pathways that influence appetite, semaglutide has the potential to significantly boost the long-term weight loss achieved through bariatric surgery alone.

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

Research has shown that semaglutide, a medication often used for weight loss, can help people lose 18% to 25% of their total body weight over approximately 68 to 88 weeks. This trial will explore its use in participants who have undergone bariatric surgery. Although bariatric surgery can lead to significant and lasting weight loss, not everyone achieves the same results. About 20% to 30% of patients either don't lose enough weight or fail to maintain it after surgery. In this trial, some participants will receive semaglutide alongside standard postoperative care, potentially providing additional support for further weight loss. ^{2 5 6 7 8}

Who Is on the Research Team?

Jaime Moore, MD MPH

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for young individuals aged 12 to 24 who have undergone bariatric surgery but haven't lost as much weight as expected within 1-2 years post-operation. It's important that participants are in the age range and at a certain stage after their surgery.

Inclusion Criteria

I am a teen with a BMI in the top 5% for my age/sex or an adult with a BMI of 30 or more.

I am willing and able to follow all study requirements.

Signed and dated informed consent form

Exclusion Criteria

Baseline alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥ 5x upper limit of normal

Baseline Creatinine >1.2mg/dL

Active major psychiatric disorder limiting informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observational

Participants complete a set of standardized measures before bariatric surgery, 3 months postoperatively, and 12 months postoperatively

12 months

3 visits (in-person)

Intervention

Participants receive usual interdisciplinary postoperative care plus weekly subcutaneous injectable semaglutide for 26 weeks

26 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview The study is examining how adolescents' bodies respond to bariatric surgery and if adding semaglutide, an injectable medication, can improve outcomes for those not meeting weight loss expectations post-surgery.

How Is the Trial Designed?

Group I: Active Medication + Standard Postoperative Care Experimental Treatment 2 Interventions

Participants can be enrolled between 1 and 2 years postoperatively and will receive usual interdisciplinary postoperative care plus weekly subcutaneous injectable semaglutide for 26 weeks. Initial dose is 0.25mg and is escalated every 4 weeks as tolerated (0.5mg, 1.0mg, 1.7mg, 2.4mg) for a total exposure of 26 weeks.

Group II: Observational Active Control 1 Intervention

Participants complete a set of standardized measures before bariatric surgery, 3 months postoperatively, and 12 months postoperatively.

Group III: Standard Postoperative Care Active Control 1 Intervention

Participants can be enrolled between 1 and 2 years postoperatively and will receive usual interdisciplinary postoperative care.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to produce the largest weight loss of any obesity medication, with an average reduction of about 15% of initial body weight over 68 weeks.

In addition to significant weight loss, semaglutide also improves cardiovascular risk factors and physical functioning, making it a promising option for chronic weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of obesity. Chao, AM., Tronieri, JS., Amaro, A., et al.[2023]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

In a study of 20 patients with type 2 diabetes in Slovenia, oral semaglutide significantly reduced HbA1c levels and fasting plasma glucose, indicating its efficacy in improving glycaemic control.

Patients reported high satisfaction with the treatment, and while some experienced mild gastrointestinal side effects, the overall safety profile was considered good, suggesting that oral semaglutide is a promising option for diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. Janić, M., Jovanović, M., Janež, A., et al.[2023]

Semaglutide, a glucagon-like peptide-1 receptor agonist, is effective for treating type 2 diabetes and obesity, providing significant weight loss and cardiovascular benefits, making it crucial for high-risk patients.

However, during the SUSTAIN clinical trial program, a safety concern arose regarding the worsening of diabetic retinopathy, potentially linked to rapid reductions in HbA1c levels, which requires further investigation and careful clinical management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide-eye-catching results. Cigrovski Berkovic, M., Strollo, F.[2023]

Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has been shown to achieve significant and sustained weight loss in individuals with obesity, surpassing results from previous weight-loss medications, and has been approved for use alongside diet and exercise.

Emerging treatments like tirzepatide and cagrilintide are demonstrating even greater weight loss effects than semaglutide, indicating a shift towards more effective 'weight-centric' strategies for managing obesity and related conditions like type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-weekly 2.4 mg Semaglutide for Weight Management in Obesity: A Game Changer? Colin, IM., Gérard, KM.[2022]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

In a study of 129 patients with severe obesity (BMI ≥ 40 kg/m²), semaglutide 2.4 mg treatment led to a significant average weight loss of 9.1% over 24 weeks, showing its effectiveness in this population.

There was no significant difference in weight loss between patients who had previously undergone bariatric surgery and those who had not, indicating that semaglutide can be a viable treatment option for both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide 2.4 mg/wk for weight loss in patients with severe obesity and with or without a history of bariatric surgery. Bonnet, JB., Tournayre, S., Anitcheou, J., et al.[2023]

In a study of 44 non-diabetic patients who experienced weight regain or insufficient weight loss after bariatric surgery, adjunct treatment with the GLP-1 receptor agonist semaglutide resulted in significant weight loss of -6.0% after 3 months and -10.3% after 6 months, indicating its efficacy in managing post-bariatric weight issues.

The study suggests that semaglutide could be a beneficial treatment option for patients struggling with weight regain after surgery, but further research through prospective randomized controlled trials is needed to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Potential of Semaglutide Once-Weekly in Patients Without Type 2 Diabetes with Weight Regain or Insufficient Weight Loss After Bariatric Surgery-a Retrospective Analysis. Lautenbach, A., Wernecke, M., Huber, TB., et al.[2022]

Citations

1. asmbs.org asmbs.org/news_releases/head-to-head-study-shows-bariatric-surgery-superior-to-glp-1-drugs-for-weight-loss/

Head-to-head Study Shows Bariatric Surgery Superior ... Patients on continuous GLP-1 therapy for a full year lost more weight, but significantly less than bariatric surgery patients (7% total weight ...

2. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2839126

Obesity Treatment With Bariatric Surgery vs GLP-1 ... Semaglutide and tirzepatide in particular have shown promising outcomes, showing 18% to 25% total weight loss within 68 to 88 weeks of treatment ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12444648/

Obesity Treatment With Bariatric Surgery vs GLP-1 ... Semaglutide and tirzepatide in particular have shown promising outcomes, showing 18% to 25% total weight loss within 68 to 88 weeks of treatment ...

4. publichealth.jhu.edu publichealth.jhu.edu/2025/one-in-seven-bariatric-surgery-patients-turn-to-new-weight-loss-drugs

One in Seven Bariatric Surgery Patients Turn to New Weight ... Despite its overall effectiveness, approximately 20% to 30% of bariatric-surgery patients' post-surgery weight loss isn't sufficient or lasting.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1550728925001881

RZY8JY68MG COMPARATIVE EFFECTIVENESS OF ... Bariatric surgery is associated with superior sustained, long term weight loss and diabetes control compared to GLP-1RAs among patients eligible for both ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa2032183

Once-Weekly Semaglutide in Adults with Overweight or ... This 68-week trial evaluated the efficacy and safety of semaglutide as compared with placebo as an adjunct to lifestyle intervention for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11906545/

Effectiveness of Adjuvant Semaglutide Following Bariatric ... The STEP trials showed that semaglutide resulted in significant weight loss in patients with and without diabetes and these effects have been ...

8. massgeneralbrigham.org massgeneralbrigham.org/en/about/newsroom/press-releases/semaglutide-before-bariatric-surgery-does-not-improve-weight-loss-or-safety

Taking Semaglutide Before Bariatric Surgery Does Not ... Mass General Brigham researchers found that total weight loss did not increase for patients who took semaglutide before having weight loss ...