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

60 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Semaglutide for PCOS?

Research shows that Semaglutide significantly reduces body weight in almost 80% of obese PCOS patients who did not respond to lifestyle changes, with many experiencing improved menstrual cycles and few side effects. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide, used under various brand names like Ozempic, Wegovy, and Rybelsus, has been shown to be generally safe in humans. In studies, it has been associated with very few side effects, and its safety profile is consistent with other similar medications, even in patients with high cardiovascular risk. ^{1 2 6 7 8}

How does the drug semaglutide differ from other treatments for PCOS?

Semaglutide is unique for PCOS treatment because it is an incretin mimetic drug that helps with weight loss and insulin resistance, which are common issues in PCOS, and it is administered as a once-weekly injection. Unlike standard lifestyle changes, semaglutide has shown significant weight loss and improvement in menstrual cycles in patients unresponsive to lifestyle modifications, with minimal side effects. ^{1 2 4 9 10}

What is the purpose of this trial?

This trial involves treating girls with obesity and polycystic ovarian syndrome using either a medication that helps control blood sugar and appetite or a specific diet plan. The goal is to reduce liver fat and improve how their bodies use insulin. This group is targeted because they are at higher risk for metabolic diseases like fatty liver and insulin resistance.

Research Team

Melanie Cree-Green, MD, PhD

Principal Investigator

Children's Hospital Colorado

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Semaglutide Treatment of Excessive Body Weight in Obese PCOS Patients Unresponsive to Lifestyle Programs. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of once-weekly semaglutide vs additional oral antidiabetic drugs in Japanese people with inadequately controlled type 2 diabetes: A randomized trial. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Liraglutide: New Perspectives for the Treatment of Polycystic Ovary Syndrome. [2020]

6. Belgium pubmed.ncbi.nlm.nih.gov

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

7. Belgium pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Diabetes Drug AIDS Weight Reduction in Adults. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Effects of Dietary Glycemic Index and Glycemic Load on Cardiometabolic and Reproductive Profiles in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials. [2023]