PCOSPhase 2/3TEALNCT03919929
Treating PCOS With Semaglutide vs Active Lifestyle Intervention
A Phase 2/3 study testing Semaglutide 3mg and 7mg [Rybelsus] and Weight loss diet in people with PCOS and Adolescent Obesity, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 21 years, women only
- Conditions the study is for
- PCOS, Adolescent Obesity, NAFLD
- What is being tested?
- Semaglutide 3mg and 7mg [Rybelsus] and Weight loss diet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 3 May 2019to 3 Oct 2023
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 21 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
- Untreated thyroid disease
- History of hypersensitivity to semaglutide
- Other causes of hyperandrogenism (example: tumor, CAH) or amenorrhea (untreated thyroid disease, tumor, primary ovarian failure, prolactinoma).
- Active symptoms or undergoing treatment for anorexia nervosa or binging/purging disorder
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Anshutz Medical Campus/Children's Hospital Colorado
Aurora, Colorado, 80045
About this study
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.
Read the 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
- Being tested
- Semaglutide 3mg and 7mg [Rybelsus], Weight loss diet
- Keywords
- Insulin Resistance
- Medical subject headings
- Pediatric Obesity, Non-alcoholic Fatty Liver Disease, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide 3mg and 7mg [Rybelsus]Drug
Also called GLP-1 receptor agonist
Once daily oral tablet of semaglutide for 4 months
Weight loss dietOther
Prescribed weight loss diet to match weight loss in Drug arm
| Study group | Role | What they receive |
|---|---|---|
| Diet Intervention | Active comparator | Weight loss with dietary intervention Receives: Other: Weight loss diet |
| GLP-1 Intervention | Experimental | Participants will take a daily oral tablet of semaglutide for 4 months. Receives: Drug: Semaglutide 3mg and 7mg [Rybelsus] |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline and 12 weeks
Secondary outcomes (3)
Change in Rate of De Novo Lipogenesis (DNL)
Change from baseline of the rate of overnight de novo lipogenesis (DNL) will be measured utilizing stable isotope methods with deuterated water, and expressed as the rate of newly synthesized lipids in the serum triglyceride fraction. A negative value means a decrease in newly synthesized lipids after the 12 week intervention, and a positive value means an increase in newly synthesized lipids after the 12 week intervention. A lower value is better.
Measured: Baseline and 12 weeks
Change in Whole Body Insulin Sensitivity
Participants will undergo a 75 gram oral glucose tolerance test, and the change from baseline in whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model.
Measured: Baseline and 12 weeks
Change in Adipose Insulin Sensitivity
Change from baseline of adipose insulin sensitivity will be calculated as the percent suppression of free fatty acids, and the nadir of free fatty acids during the oral glucose tolerance test. Percent suppression of FFAs during the OGTT was calculated as fasting FFA minus the minimal FFA value divided by fasting FFA. This was calculated for baseline and after 12-weeks of intervention. The change was calculated by subtracting the final-baseline values. A higher absolute value means there was an improvement in adipose insulin sensitivity after 12-weeks of treatment.
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2019
- Study start3 May 2019
- Primary completion3 Oct 2023
- Study completion3 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PCOSStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Melanie Cree-Green, MD, PhD, Principal investigator, Children's Hospital Colorado
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03919929
- Sponsor's protocol ID
- 19-0636
- Other IDs
- 1R01DK120612-01A1
- Acronym
- TEAL
- Status last verified
- Nov 2025
- First submitted
- 15 Apr 2019
- Last updated
- 25 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Boster JM, Cree MG, Kelsey MM, Nadeau KJ, Chaidez A, Pan Z, Sundaram SS. Relative Skeletal Muscle Mass Is Associated With Hepatic Steatosis in Adolescents With Overweight and Obesity. Pediatr Obes. 2026 Apr;21(4):e70108. doi: 10.1111/ijpo.70108.
PubMed 42014131