Semaglutide for Polycystic Ovary Syndrome

(RESTORE Trial)

Overseen by Melanie Cree-Green, MD,PhD

Age: < 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial involves girls and women aged 12-35 with obesity and PCOS taking a medication that helps manage blood sugar and promote weight loss. The goal is to see if this treatment can improve their weight and reproductive health.

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.

What data supports the effectiveness of the drug semaglutide for treating polycystic ovary syndrome (PCOS)?

Research shows that semaglutide helps reduce body weight in nearly 80% of obese PCOS patients who did not respond to lifestyle changes, with many also experiencing normalized menstrual cycles and improved blood sugar levels. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide has been studied for safety in various conditions, including obesity and type 2 diabetes, and is generally considered safe with few side effects. In a study with obese PCOS patients, very few side effects were reported. Additionally, in trials for type 2 diabetes, semaglutide showed a tolerability profile consistent with other similar medications and was not inferior to placebo in terms of cardiovascular safety. ^{1 3 4 5 6}

How is the drug semaglutide unique for treating polycystic ovary syndrome (PCOS)?

Semaglutide is unique for treating PCOS because it is a once-weekly injection that not only helps with weight loss in patients unresponsive to lifestyle changes but also improves insulin resistance and normalizes menstrual cycles, with minimal side effects. ^{1 2 6 7 8}

Research Team

Melanie Cree-Green, MD,PhD

Principal Investigator

University of Colorado Anschutz/Children's Hospital Colorado

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Semaglutide (Glucagon-like peptide-1 receptor agonist)

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.

Participant Groups

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 Canada, Japan for the following indications:

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Aviva Abosch

University of Colorado, Denver

Chief Medical Officer since 2019

MD

Uday B. Kompella

University of Colorado, Denver

Chief Executive Officer since 2015

PhD in Pharmaceutical Sciences

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

Collaborator

Trials

2,103

Recruited

2,760,000+

Dr. Diana W. Bianchi

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

Chief Executive Officer since 2016

MD from Stanford University

Dr. Alison Cernich

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

Chief Medical Officer since 2020

PhD in Clinical Psychology from University of Maryland

Findings from Research

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]

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]

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]

References

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

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

2. Belgium pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

5. England 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. [2022]

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

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

7. England pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Integrating oral semaglutide into clinical practice in primary care: for whom, when, and how? [2020]