Semaglutide for Polycystic Ovary Syndrome

(RESTORE Trial)

Overseen By Yesenia Garcia-Reyes, MS

Age: < 65

Sex: Female

Trial Phase: Phase 3

Sponsor: University of Colorado, Denver

Must be taking: Metformin

Must not be taking: Steroids, Antipsychotics, HIV meds, others

Disqualifiers: Thyroid cancer, Diabetes, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 40 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for girls and women with polycystic ovary syndrome (PCOS) who also face obesity. The researchers aim to determine if the medication semaglutide (known as Ozempic, Wegovy, or Rybelsus) can improve metabolism, aid in weight loss, and address reproductive issues linked to PCOS. Participants will be grouped based on their use of metformin and will receive semaglutide for 10 months. Suitable candidates have PCOS, are not very active, and experience irregular periods, with or without metformin treatment. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for PCOS.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot use certain medications like hormonal contraception, weight loss drugs, or medications affecting insulin sensitivity. If you're on metformin, you must have been stable on it for at least 3 months before joining the trial.

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

Research shows that semaglutide is generally safe for people with polycystic ovary syndrome (PCOS). Studies indicate that low doses of semaglutide help nearly 80% of obese PCOS patients lose weight. It also reduces waist size, body mass index (BMI), and certain hormone levels, like testosterone, which benefits women with PCOS.

However, like any medication, semaglutide may cause side effects. Some reports mention risks related to anesthesia because it can slow stomach emptying. Overall, it is considered safe for treating conditions like type 2 diabetes and PCOS, indicating a strong safety record for these conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PCOS?

Semaglutide is unique because it offers a new approach to treating polycystic ovary syndrome (PCOS) by targeting the GLP-1 receptor, which can help regulate insulin levels and improve metabolic function. Unlike traditional treatments like metformin and hormonal therapies that primarily focus on insulin resistance and menstrual regulation, semaglutide may also aid in weight management, an important factor for many with PCOS. Researchers are excited about semaglutide's potential to address multiple symptoms of PCOS in one treatment, offering a comprehensive approach to managing this complex condition.

What evidence suggests that semaglutide might be an effective treatment for PCOS?

Research has shown that semaglutide effectively aids weight loss in individuals with polycystic ovary syndrome (PCOS). Studies have found that nearly 80% of obese PCOS patients who did not achieve results from lifestyle changes lost weight with this treatment. In this trial, participants will receive semaglutide either alone or combined with metformin. Semaglutide also enhances insulin use, which is crucial for managing PCOS. When combined with metformin, semaglutide significantly reduces body weight and blood sugar levels more than metformin alone. Additionally, semaglutide improves body mass index (BMI) and cholesterol levels, especially at higher doses, benefiting those with PCOS. ^{1 6 7 8 9}

Who Is on the Research Team?

Melanie Cree-Green, MD,PhD

Principal Investigator

University of Colorado Anschutz/Children's Hospital Colorado

Are You a Good Fit for This Trial?

This trial is for girls and women aged 12-35 with obesity and polycystic ovary syndrome (PCOS), who may or may not be taking metformin. Participants should exercise less than 2 hours a week, have irregular periods, and meet specific PCOS criteria. They must not use hormonal contraception but can use non-hormonal methods.

Inclusion Criteria

I have infrequent menstrual periods as defined by the latest PCOS guidelines.

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

I have been diagnosed with PCOS following strict NIH criteria, including irregular periods or high testosterone.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observation

Participants undergo a 4-month observation period with either no medication or metformin treatment

16 weeks

Treatment

Participants receive 10 months of semaglutide intervention to induce metabolic changes, weight loss, and improve reproductive abnormalities

40 weeks

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 tests the effects of Semaglutide (Wegovy) on metabolic changes, weight loss, and reproductive health in participants with PCOS over 10 months. Some will also continue their metformin treatment if they've been stable on it for at least three months.

How Is the Trial Designed?

Group I: Untreated PCOS Experimental Treatment 1 Intervention

Participants with PCOS who are not on metformin or hormonal therapy, will receive 10-months of semaglutide intervention. Participants will get either semaglutide as either: Wegovy: 0.25mg for 4 weeks, 0.5mg for 4 weeks, 1mg 4-weeks, and 1.7mg for the remainder of the study. or Ozempic: 0.25mg for 4 weeks, 0.5mg for 4 weeks, 1mg 4-weeks, and Wegovy for 1.7mg for the remainder of the study.

Group II: PCOS on Metformin Experimental Treatment 1 Intervention

Participants with PCOS who are currently on metformin and still not having regular menses, will receive 10-months of semaglutide intervention. Participants in this arm will continue to take their metformin throughout the trial. Participants will get either semaglutide as either: Wegovy: 0.25mg for 4 weeks, 0.5mg for 4 weeks, 1mg 4-weeks, and 1.7mg for the remainder of the study. or Ozempic: 0.25mg for 4 weeks, 0.5mg for 4 weeks, 1mg 4-weeks, and Wegovy for 1.7mg for the remainder of the study.

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+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

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]

Semaglutide, a GLP-1 receptor agonist for type 2 diabetes, has a good safety profile but is associated with a high prevalence of gastrointestinal disorders, reported in over 3500 cases (53.2%).

Compared to other diabetes medications like sitagliptin and empagliflozin, semaglutide has a significantly higher number of reported gastrointestinal adverse events, indicating the need for careful monitoring in certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. Cabral Lopes, A., Roque, F., Lourenço, O., et al.[2023]

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]

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]

Oral semaglutide is the first FDA-approved oral GLP-1 receptor agonist for type 2 diabetes, showing effectiveness in reducing blood sugar levels and body weight in patients with uncontrolled diabetes, while maintaining a safety profile similar to injectable GLP-1RAs.

It is particularly beneficial for patients with inadequate glycemic control on other medications, those needing weight loss, and those at risk of hypoglycemia, but it is contraindicated in individuals with a history of certain thyroid cancers and pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating oral semaglutide into clinical practice in primary care: for whom, when, and how? Brunton, SA., Mosenzon, O., Wright, EE.[2020]

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 significantly reduced HbA1c levels in Japanese patients by 1.0% to 1.7% depending on the dosage, showing greater or similar efficacy compared to other diabetes medications.

The treatment also led to notable body weight reductions of up to 4.7%, with gastrointestinal side effects being the most common but generally mild to moderate, indicating that it is well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 trials. Araki, E., Terauchi, Y., Watada, H., 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12504844/

The dual impact of GLP-1 receptor agonists on metabolic and ... Among these, GLP-1RAs are increasingly being used to treat PCOS due to their efficacy in improving insulin sensitivity, encouraging weight ...

3. 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 ...

4. 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 ...

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. 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11790292/

Semaglutide: Double-edged Sword with Risks and Benefits Semaglutide can also be used to treat chronic kidney disease and polycystic ovary syndrome. Semaglutide therapy has adverse anesthetic risks due to delayed ...

8. goodrx.com goodrx.com/conditions/pcos/ozempic-and-pcos?srsltid=AfmBOorn3toQbLlTx-3aU2SFC12GICABxTkgm8JaYQZgjPz-hqv9n4zm

Ozempic and PCOS: What Are the Benefits and Risks? You can safely take Ozempic (semaglutide) to treat Type 2 diabetes if you have polycystic ovary syndrome (PCOS). PCOS is a complex hormone ...

9. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05646199

Semaglutide vs Metformin in Polycystic Ovary Syndrome ... The goal of this clinical trial is to compare the effect of Semaglutide and metformin on weight loss in obese women with Polycystic Ovarian Syndrome (PCOS) ...