Semaglutide for Obesity

(STABLE Wt Loss Trial)

Overseen By Kaitlyn DeRouen, BA, BSEd

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Pennsylvania

Must not be taking: Weight loss drugs, Oral steroids

Disqualifiers: Diabetes, Severe depression, Substance abuse, 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: 168

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called semaglutide (a subcutaneous solution) to assess its effects on eating habits and appetite in individuals seeking weight loss. Participants will receive either semaglutide or a placebo (an inactive solution) for 72 weeks, along with diet and exercise guidance. The trial seeks individuals who are noticeably overweight (BMI of 30 or more) or have weight-related health issues like high blood pressure or sleep apnea. As a Phase 4 trial, this research aims to understand how this FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have changed their chronic medication type or dosage in the past 3 months. It also excludes those who have used medications known to affect weight in the last 6 months.

What is the safety track record for these treatments?

Research has shown that semaglutide, the medication under study, is generally safe for individuals who are overweight or obese. Many participants in studies lost significant weight without experiencing serious side effects. Some reported mild to moderate side effects, such as nausea or digestive issues, but these were uncommon.

Losing weight quickly with semaglutide can slightly increase the risk of gallbladder problems, like gallstones. However, these risks remain low and are monitored during treatment.

The FDA has already approved semaglutide for weight loss, indicating that its safety has been thoroughly reviewed for this purpose. Overall, evidence supports semaglutide as a safe option for most people seeking to lose weight. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for obesity, which often involve lifestyle changes and medications that target appetite or absorption, semaglutide stands out because it's a GLP-1 receptor agonist. This means it mimics a hormone that helps regulate appetite and food intake, leading to significant weight loss. Researchers are excited about semaglutide, particularly in its subcutaneous form, because it has shown promising results in producing more substantial and sustained weight loss compared to other options. Additionally, its once-weekly injection offers a convenient alternative to daily medications, potentially improving adherence and outcomes.

What is the effectiveness track record for semaglutide in treating obesity?

Research has shown that semaglutide aids weight loss in people with obesity. In one study, participants taking semaglutide lost an average of 14.9% of their body weight after 68 weeks, while those on a placebo lost only 2.4%. Another study found that up to half of the participants lost at least 20% of their weight over two years. Additionally, semaglutide reduces the risk of major heart-related problems by 20% in people with obesity. The FDA has approved this treatment for weight loss, underscoring its proven effectiveness. In this trial, participants will receive either semaglutide with behavioral treatment or a placebo with behavioral treatment to evaluate the effectiveness of these combinations. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults aged 18-70 wanting to lose weight, with a BMI ≥ 30 or ≥ 27 with obesity-related health issues. Must not be pregnant, able to consent, and plan to stay in Philadelphia for the study duration. Excludes those with uncontrolled diabetes or hypertension, recent pancreatitis or cancer history, severe psychiatric disorders, recent weight loss drugs use, and certain cardiovascular conditions.

Inclusion Criteria

Plan to remain in the Philadelphia area for the next 1.5 years.

non-pregnant, evidenced by a negative urine pregnancy test

Eligible female patients will be: non-pregnant, evidenced by a negative urine pregnancy test

Exclusion Criteria

I was diagnosed with bulimia nervosa in the last 5 years.

I have not taken weight-altering or GLP-1 drugs in the last 6 months.

I have had acute pancreatitis in the past 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Study 1)

Participants receive semaglutide or placebo with lifestyle intervention for 60 weeks

60 weeks

Visits at baseline, weeks 20, 40, and 60

Re-randomized Medication Withdrawal (Study 2)

Semaglutide-treated subjects are re-randomized to semaglutide or placebo for 12 weeks

12 weeks

Final assessment at week 72

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Final safety visit at week 76

What Are the Treatments Tested in This Trial?

Interventions

• Behavioral Treatment
• Placebo
• Semaglutide 2.4 MG/0.75 ML Subcutaneous Solution [WEGOVY]

Trial Overview The trial tests if semaglutide affects appetite and eating habits over time compared to a placebo. Participants also receive lifestyle advice on diet and exercise. Semaglutide is an FDA-approved medication for weight loss administered subcutaneously for 72 weeks alongside behavioral treatment.

How Is the Trial Designed?

Group I: Behavioral Treatment + Placebo Active Control 2 Interventions

Behavioral treatment (lifestyle modification counseling for weight loss) plus placebo

Group II: Behavioral Treatment + Medication Active Control 2 Interventions

Behavioral treatment (lifestyle modification counseling for weight loss) plus semaglutide

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Novo Nordisk A/S

Industry Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

High-dose once-weekly semaglutide has been shown to significantly reduce weight in patients with obesity or overweight, as demonstrated in four phase 3 clinical trials involving various populations, including those with diabetes.

While gastrointestinal side effects were common, semaglutide was generally well tolerated and also led to improvements in cardiometabolic risk factors, such as waist circumference and blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. Bradley, CL., McMillin, SM., Hwang, AY., et al.[2022]

Subcutaneous semaglutide (Wegovy) has been shown to significantly reduce body weight in overweight and obese individuals, with a dose-dependent effect observed in four Phase 3 trials involving 5000 participants.

While semaglutide resulted in greater weight loss compared to placebo, gastrointestinal side effects were the most common safety concerns, highlighting the need for further studies in diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical review of subcutaneous semaglutide for obesity. Phillips, A., Clements, JN.[2022]

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 meta-analysis of six randomized controlled trials involving 3962 overweight or obese individuals, subcutaneous semaglutide 2.4 mg administered weekly resulted in significant and sustainable weight loss, with an average reduction of 11.8% in body weight compared to placebo.

Semaglutide was well tolerated, with the most common side effects being mild to moderate gastrointestinal issues, indicating a favorable safety profile for non-diabetic overweight or obese individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta-analysis including the 2-year STEP 5 trial. Qin, W., Yang, J., Deng, C., et al.[2023]

A survey of 127 physicians revealed that many have varying pre-treatment requirements for prescribing semaglutide for weight loss, with 30% requiring a minimum body mass index of 30 kg/m² and 67% expecting documented lifestyle changes.

Despite its effectiveness, over 50% of patients discontinued semaglutide therapy within the first 3 months, primarily due to cost, perceived lack of effectiveness, and concerns about long-term side effects, indicating a need for better patient education and support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Semaglutide Use for Weight Management: Practice and Attitudes of Physicians in Israel. Dicker, D., Tamir, O., Lieberman-Segal, G., et al.[2023]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5476722/

Cognitive behavioral therapy to aid weight loss in obese ... A cognitive-behavioral therapeutic program for patients with obesity and binge eating disorder: short- and long-term follow-up data of a prospective study.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-10565

Cognitive Behavioral Therapy for Insomnia Compared to ... CBT-I plus BWL may be more effective than EDU plus BWL in improving sleep, weight loss and body composition in overweight or obese women with breast DCIS or ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3258572/

Cognitive-Behavioral Therapy, Behavioral Weight Loss ... Mixed models analyses revealed that CBT produced significantly greater reductions in binge-eating than BWL through 12-month follow-ups and that BWL produced ...

4. bpsmedicine.biomedcentral.com bpsmedicine.biomedcentral.com/articles/10.1186/s13030-020-00177-9

Personalized cognitive-behavioural therapy for obesity (CBT ... In that study, 77 patients with morbid obesity who completed the treatment achieved 9.9% weight loss after 18 months. These promising results, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0195666325001758

Effect of a cognitive behavioural therapy intervention to ... In conclusion, this study demonstrates that a CBTi intervention leads to improvements in food craving control and changes in food preference.

6. novomedlink.com novomedlink.com/obesity/products/treatments/wegovy/efficacy-safety/safety-profile.html

Wegovy® Safety Profile Learn about the safety profile of Wegovy® after being evaluated in clinical studies. Read Important Safety and Prescribing Info, including Boxed Warning.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/215256s011lbl.pdf

WEGOVY (semaglutide) injection, for subcutaneous use Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in WEGOVY-treated ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38016699/

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.

9. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/wegovy

Wegovy | European Medicines Agency (EMA) After 68 weeks, those treated with Wegovy were able on average to lose 10% of their weight compared with a 3% loss in people who had placebo. In addition, 67% ...

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

Once-Weekly Semaglutide in Adults with Overweight or ... 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight.