Treating PCOS With Semaglutide vs Active Lifestyle Intervention

NCT03919929 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 19-06361R01DK120612-01A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

PCOS; Adolescent Obesity; NAFLD

Keywords

Insulin Resistance

Outcome Measures

Primary Outcomes (2)

• Change in Hepatic Fat Fraction

  Change from baseline in presence/severity of hepatic fat fraction will be measured with MRI, and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. A negative value means a decrease in liver fat, and a positive value means an increase in liver fat.

  Baseline and 12 weeks

• Change in Weight

  Change in weight will be calculated for each group (diet and semaglutide), and both the absolute and relative weight changes between the two groups will be reported.

  Baseline and 12 weeks

Secondary Outcomes (3)

• Change in Rate of De Novo Lipogenesis (DNL)

  Baseline and 12 weeks

• Change in Whole Body Insulin Sensitivity

  Baseline and 12 weeks

• Change in Adipose Insulin Sensitivity

  Baseline and 12 weeks

Other Outcomes (2)

• Change in Percentage of Indirect Glycerol Carbon Contributions to Newly Synthesized Triglycerides and Glucose

  Baseline and 12 weeks

• Change in Free Androgen Index

  Baseline and 12 weeks

Study Arms (2)

Diet Intervention

ACTIVE COMPARATOR

Weight loss with dietary intervention

Other: Weight loss diet

GLP-1 Intervention

EXPERIMENTAL

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

Drug: Semaglutide 3mg and 7mg [Rybelsus]

Interventions

Semaglutide 3mg and 7mg [Rybelsus] DRUG

Once daily oral tablet of semaglutide for 4 months

Also known as: GLP-1 receptor agonist

GLP-1 Intervention

Weight loss diet OTHER

Prescribed weight loss diet to match weight loss in Drug arm

Diet Intervention

Eligibility Criteria

• Age: 12 Years - 21 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Sedentary- less than 2 hours of moderate (jogging, swimming etc) exercise a week.
• BMI equal or greater than the 90th percentile for age and gender
• PCOS per the most stringent NIH criteria adapted for adolescents (irregular menses \>12 months post-menarche and clinical or biochemical hypertestosteronemia
• 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.

You may not qualify if:

• 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.
• 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.
• Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
• Severe illness requiring hospitalization within 60 days.
• Diabetes, defined as Hemoglobin A1C \> 6.4%
• BMI percentile less than the 90th percentile for age and sex. Weight \>325 lbs. or \<84 lbs.
• Anemia, defined as Hemoglobin \< 11 mg/dL
• Diagnosed major psychiatric or developmental disorder limiting informed consent.
• Implanted metal devices that are not compatible with MRI
• Use of blood pressure medications.
• Known liver disease other than NAFLD or AST or ALT \>100 IU/L.
• Personal history of pancreatitis
• Known renal disease of any severity or an eGFR at screening of \<45ml/min/1.73m2
• History of severe GI disease (e.g. gastroparesis)
• History of gallstones

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

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

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Pediatric Obesity; Non-alcoholic Fatty Liver Disease; Insulin Resistance

Interventions

semaglutide; Diet, Reducing

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fatty Liver; Liver Diseases; Digestive System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Results Point of Contact

• Title: Melanie Cree, MD, PhD
• Organization: University of Colorado Anschutz Medical Campus

melanie.cree@childrenscolorado.org

720-777-5743

Study Officials

• Melanie Cree-Green, MD, PhD

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: April 18, 2019
• Study Start: May 3, 2019
• Primary Completion: October 3, 2023
• Study Completion: October 3, 2023
• Last Updated: November 25, 2025
• Results First Posted: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)