Treating PCOS With Semaglutide vs Active Lifestyle Intervention

NCT ID: NCT03919929

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-03
• Study Completion Date: 2023-10-03

Brief Summary

Girls with obesity and polycystic ovarian syndrome will receive either glucagon like peptide-1 receptor agonist therapy or a dietary intervention for 12 weeks to decrease the metabolic syndrome, in particular to lower hepatic fat and improve insulin sensitivity.

Detailed Description

In obese girls with polycystic ovarian syndrome, testosterone and obesity combine to create unique pathology to increase metabolic disease including fatty liver and insulin resistance, which may be mediated by altered glucagon like peptide-1 activity. The investigators will treat girls with obesity and polycystic ovarian syndrome for 4 months with a glucagon like peptide-1 receptor agonist compared to dietary intervention to primarily lower hepatic fat and secondarily improve whole body and adipose insulin sensitivity. Mechanisms of hepatic metabolism, including rates of de novo lipogenesis and relative mitochondrial flux will also be assessed.

Conditions

PCOS; Adolescent Obesity; NAFLD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Diet Intervention

Weight loss with dietary intervention

Group Type: ACTIVE_COMPARATOR

Weight loss diet

Intervention Type: OTHER

Prescribed weight loss diet to match weight loss in Drug arm

GLP-1 Intervention

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

Group Type: EXPERIMENTAL

Semaglutide 3mg and 7mg [Rybelsus]

Intervention Type: DRUG

Once daily oral tablet of semaglutide for 4 months

Interventions

Semaglutide 3mg and 7mg [Rybelsus]

Once daily oral tablet of semaglutide for 4 months

Intervention Type: DRUG

Weight loss diet

Prescribed weight loss diet to match weight loss in Drug arm

Intervention Type: OTHER

Other Intervention Names

GLP-1 receptor agonist

Eligibility Criteria

Inclusion Criteria

1. Sedentary- less than 2 hours of moderate (jogging, swimming etc) exercise a week.

2. BMI equal or greater than the 90th percentile for age and gender

3. PCOS per the most stringent NIH criteria adapted for adolescents (irregular menses >12 months post-menarche and clinical or biochemical hypertestosteronemia

4. Participants cannot be on hormonal contraception, so participants should remain abstinent or use reliable non-hormonal contraception (e.g. copper IUD) for the entire study period. For participants who receive semaglutide, they should avoid pregnancy for at least 2 months after stopping medication to avoid fetal exposure to the medication.

Exclusion Criteria

1. Diagnosed with or have a family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Family history of medullary thyroid cancer or thyroid nodule palpated by endocrinologist at screening.

2. Use of medications known to affect insulin sensitivity: metformin (cannot have been used in the 3 months prior to screening), oral glucocorticoids within 10 days, atypical antipsychotics, immunosuppressant agents, HIV medications, hormonal contraception (cannot have been used in the 6 months prior to screening). Dermal patch or vaginal ring contraception methods.Weight loss medications or stimulants. Use of other products containing other GLP-1 agonists.

3. Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.

4. Severe illness requiring hospitalization within 60 days.

5. Diabetes, defined as Hemoglobin A1C > 6.4%

6. BMI percentile less than the 90th percentile for age and sex. Weight >325 lbs. or <84 lbs.

7. Anemia, defined as Hemoglobin < 11 mg/dL

8. Diagnosed major psychiatric or developmental disorder limiting informed consent.

9. Implanted metal devices that are not compatible with MRI

10. Use of blood pressure medications.

11. Known liver disease other than NAFLD or AST or ALT >100 IU/L.

12. Personal history of pancreatitis

13. Known renal disease of any severity or an eGFR at screening of <45ml/min/1.73m2

14. History of severe GI disease (e.g. gastroparesis)

15. History of gallstones

16. Untreated thyroid disease

17. History of hypersensitivity to semaglutide

18. Other causes of hyperandrogenism (example: tumor, CAH) or amenorrhea (untreated thyroid disease, tumor, primary ovarian failure, prolactinoma).

19. Active symptoms or undergoing treatment for anorexia nervosa or binging/purging disorder

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melanie Cree-Green, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Colorado

Locations

University of Colorado Anshutz Medical Campus/Children's Hospital Colorado

Aurora, Colorado, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R01DK120612-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

19-0636

Identifier Type: -

Identifier Source: org_study_id