Semaglutide vs Lifestyle Changes for PCOS

(TEAL Trial)

Overseen By Yesenia Garcia-Reyes, MS

Age: < 65

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: University of Colorado, Denver

Must not be taking: Metformin, Antipsychotics, HIV medications, others

Disqualifiers: Pregnancy, Diabetes, Thyroid disease, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication, semaglutide (also known as Ozempic, Wegovy, or Rybelsus), against lifestyle changes to help girls with obesity and polycystic ovarian syndrome (PCOS) improve their health. The goal is to reduce liver fat and increase insulin sensitivity, which can help manage PCOS symptoms. Participants will either take a daily semaglutide tablet or follow a special diet for 12 weeks. Girls with irregular periods for over a year and who exercise less than two hours a week might be a good fit for this trial. As a Phase 2 and Phase 3 trial, this study is crucial for measuring semaglutide's effectiveness and is in the final step before FDA approval, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that affect insulin sensitivity, such as metformin, oral glucocorticoids, atypical antipsychotics, immunosuppressants, HIV medications, hormonal contraception, weight loss medications, stimulants, and other GLP-1 agonists. If you are on any of these, you would need to stop them before participating.

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

Research has shown that semaglutide, a type of medication, is generally safe for people with polycystic ovarian syndrome (PCOS). Studies have found that semaglutide not only aids in weight loss but is also well-tolerated. In one study, about 80% of obese women with PCOS lost a significant amount of weight using semaglutide. Another study confirmed that medications like semaglutide are safe and effective for women with PCOS, helping to improve body mass index (BMI), triglycerides, and waist size. While some side effects might occur, current evidence suggests that semaglutide is a promising option for weight loss in PCOS without major safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for PCOS focus on lifestyle changes, like diet and exercise, or medications that regulate hormones. But semaglutide works differently, targeting the GLP-1 receptor to help control insulin levels and reduce appetite. Researchers are excited about semaglutide because it is administered as an oral tablet, making it easier to take than some injectable options. This novel approach not only aids in weight loss but also directly addresses insulin resistance, a key factor in PCOS.

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

Research has shown that semaglutide, which participants in this trial may receive, can help treat polycystic ovarian syndrome (PCOS) by aiding in weight loss and improving overall health. One study found that nearly 80% of women with PCOS who were overweight lost weight when taking semaglutide, especially those who didn't see results from diet and exercise alone. Another study found that semaglutide reduced waist size, body mass index (BMI), and certain blood fats in women with PCOS. It also improved how the body uses insulin, which is important for managing PCOS. Overall, these findings suggest that semaglutide could be a promising option for managing PCOS symptoms related to weight and health. Meanwhile, another group in this trial will follow a weight loss diet to compare the effectiveness of lifestyle changes alone. ^{1 2 5 6 7}

Who Is on the Research Team?

Melanie Cree-Green, MD, PhD

Principal Investigator

Children's Hospital Colorado

Are You a Good Fit for This Trial?

This trial is for girls with obesity and PCOS who are in the top 10% of weight for their age and gender, don't exercise much, aren't on hormonal birth control, and can avoid pregnancy. It's not for those who are pregnant or breastfeeding, have diabetes or severe illnesses, take certain medications affecting insulin sensitivity, or have specific medical conditions like liver disease.

Inclusion Criteria

My BMI is in the top 10% for my age and gender.

I have PCOS, diagnosed with irregular periods and high testosterone.

I am not using hormonal birth control and will use non-hormonal methods or abstain during the study.

Exclusion Criteria

You have had a bad reaction to semaglutide in the past.

I have a severe stomach or intestine condition.

I have not been hospitalized for a severe illness in the last 60 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either semaglutide or dietary intervention for 12 weeks to decrease metabolic syndrome

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide
• Weight loss diet

Trial Overview The study compares two approaches to treat metabolic issues caused by obesity and PCOS: one group will receive Semaglutide (a medication), while another will follow a weight loss diet. The goal is to reduce liver fat and improve how the body uses insulin over a period of 12 weeks.

How Is the Trial Designed?

Group I: GLP-1 Intervention Experimental Treatment 1 Intervention

Participants will take a daily oral tablet of semaglutide for 4 months.

Group II: Diet Intervention Active Control 1 Intervention

Weight loss with dietary intervention

Semaglutide is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Wegovy for:

• Obesity

Approved in United States as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

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 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, marketed as Rybelsus, is the first oral glucagon-like peptide receptor agonist approved by the FDA in 2019 for treating type 2 diabetes, highlighting its innovative delivery method.

This medication, taken once daily, aids in glucose control and weight management, potentially leading to improved health outcomes for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. Blakely, KK., Weaver, K.[2021]

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 27 obese patients with PCOS who did not respond to lifestyle modifications, treatment with semaglutide led to an average weight loss of 7.6 kg after three months, with 80% of participants achieving at least a 5% reduction in body weight.

Semaglutide treatment not only resulted in significant weight loss but also improved insulin sensitivity and normalized menstrual cycles in 80% of responsive patients, all with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Treatment of Excessive Body Weight in Obese PCOS Patients Unresponsive to Lifestyle Programs. Carmina, E., Longo, RA.[2023]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10531549/

Semaglutide Treatment of Excessive Body Weight in ... Treatment with semaglutide, at low doses, significantly reduces body weight in almost 80% of obese PCOS patients who were unresponsive to a previous lifestyle ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05646199

Semaglutide vs Metformin in Polycystic Ovary Syndrome ... In patients with type 2 diabetes, there was ≥5% weight loss in 63% of patients treated with Semaglutide. On the other hand, liraglutide has shown around 5-7 kg ...

3. rbej.biomedcentral.com rbej.biomedcentral.com/articles/10.1186/s12958-025-01447-3

Effects of combined metformin and semaglutide therapy on ... The results indicate that the combination therapy significantly reduced body weight and FBG levels compared to MET monotherapy, though it did ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1056872724001600

The efficacy and safety of GLP-1 agonists in PCOS women ... In summary, GLP1-RAs can reduce waist circumference, BMI, serum triglycerides and total testosterone in women with polycystic ovarian syndrome (PCOS). This ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/09513590.2025.2553052

Meta-analysis of the effects of semaglutide on body mass ... Semaglutide significantly improves BMI and lipid profiles in PCOS, particularly at higher doses, and in obese patients. Further long-term studies are needed to ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39178623/

The efficacy and safety of GLP-1 agonists in PCOS women ... The use of GLP1-RAs demonstrates efficacy in reducing BMI, triglycerides, waist circumference and total testosterone.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05646199

Semaglutide vs Metformin in Polycystic Ovary Syndrome ... Treatment with Semaglutide will result in significant weight loss compared to metformin and that will be associated with significant improvements in hormonal ...