Trial Outcomes & Findings for Treating PCOS With Semaglutide vs Active Lifestyle Intervention (NCT NCT03919929)
NCT ID: NCT03919929
Last Updated: 2025-11-25
Results Overview
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.
COMPLETED
PHASE2/PHASE3
60 participants
Baseline and 12 weeks
2025-11-25
Participant Flow
There were 5 participants who screen failed, and 4 participants who withdrew due to not tolerating the study medication.
Participant milestones
| Measure |
Diet Intervention
Weight loss with dietary intervention
Weight loss diet: 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.
Semaglutide 3mg and 7mg \[Rybelsus\]: Once daily oral tablet of semaglutide for 4 months
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
43
|
|
Overall Study
COMPLETED
|
17
|
34
|
|
Overall Study
NOT COMPLETED
|
0
|
9
|
Reasons for withdrawal
| Measure |
Diet Intervention
Weight loss with dietary intervention
Weight loss diet: 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.
Semaglutide 3mg and 7mg \[Rybelsus\]: Once daily oral tablet of semaglutide for 4 months
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
4
|
|
Overall Study
Screen Failure
|
0
|
5
|
Baseline Characteristics
Treating PCOS With Semaglutide vs Active Lifestyle Intervention
Baseline characteristics by cohort
| Measure |
Diet Intervention
n=17 Participants
Weight loss with dietary intervention
Weight loss diet: Prescribed weight loss diet to match weight loss in Drug arm
|
GLP-1 Intervention
n=38 Participants
Participants will take a daily oral tablet of semaglutide for 4 months.
Semaglutide 3mg and 7mg \[Rybelsus\]: Once daily oral tablet of semaglutide for 4 months
|
Total
n=55 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
14.44 years
STANDARD_DEVIATION 1.55 • n=45 Participants
|
15.65 years
STANDARD_DEVIATION 1.71 • n=12929 Participants
|
15.20 years
STANDARD_DEVIATION 1.64 • n=6349 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=45 Participants
|
38 Participants
n=12929 Participants
|
55 Participants
n=6349 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=45 Participants
|
0 Participants
n=12929 Participants
|
0 Participants
n=6349 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=45 Participants
|
18 Participants
n=12929 Participants
|
27 Participants
n=6349 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=45 Participants
|
20 Participants
n=12929 Participants
|
28 Participants
n=6349 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=45 Participants
|
0 Participants
n=12929 Participants
|
0 Participants
n=6349 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=45 Participants
|
38 participants
n=12929 Participants
|
55 participants
n=6349 Participants
|
PRIMARY outcome
Timeframe: Baseline and 12 weeksChange 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.
Outcome measures
| Measure |
GLP-1 Intervention
n=34 Participants
Participants will take a daily oral tablet of semaglutide for 4 months.
Semaglutide 3mg and 7mg \[Rybelsus\]: Once daily oral tablet of semaglutide for 4 months
|
Diet Intervention
n=17 Participants
Weight loss with dietary intervention
Weight loss diet: Prescribed weight loss diet to match weight loss in Drug arm
|
|---|---|---|
|
Change in Hepatic Fat Fraction
|
-1.84 Change in percentage of liver fat
Standard Deviation 4.39
|
-1.41 Change in percentage of liver fat
Standard Deviation 2.24
|
PRIMARY outcome
Timeframe: Baseline and 12 weeksChange 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.
Outcome measures
| Measure |
GLP-1 Intervention
n=34 Participants
Participants will take a daily oral tablet of semaglutide for 4 months.
Semaglutide 3mg and 7mg \[Rybelsus\]: Once daily oral tablet of semaglutide for 4 months
|
Diet Intervention
n=17 Participants
Weight loss with dietary intervention
Weight loss diet: Prescribed weight loss diet to match weight loss in Drug arm
|
|---|---|---|
|
Change in Weight
|
-5.30 Change in weight (KG)
Standard Deviation 4.92
|
-1.66 Change in weight (KG)
Standard Deviation 2.81
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksChange 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.
Outcome measures
| Measure |
GLP-1 Intervention
n=34 Participants
Participants will take a daily oral tablet of semaglutide for 4 months.
Semaglutide 3mg and 7mg \[Rybelsus\]: Once daily oral tablet of semaglutide for 4 months
|
Diet Intervention
n=17 Participants
Weight loss with dietary intervention
Weight loss diet: Prescribed weight loss diet to match weight loss in Drug arm
|
|---|---|---|
|
Change in Rate of De Novo Lipogenesis (DNL)
|
-1.9 mg/dL
Standard Deviation 1.0
|
0.94 mg/dL
Standard Deviation 5.7
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksParticipants 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.
Outcome measures
| Measure |
GLP-1 Intervention
n=34 Participants
Participants will take a daily oral tablet of semaglutide for 4 months.
Semaglutide 3mg and 7mg \[Rybelsus\]: Once daily oral tablet of semaglutide for 4 months
|
Diet Intervention
n=17 Participants
Weight loss with dietary intervention
Weight loss diet: Prescribed weight loss diet to match weight loss in Drug arm
|
|---|---|---|
|
Change in Whole Body Insulin Sensitivity
|
0.000213 dl/kg/min per microU/ml
Standard Deviation 0.000423
|
0.0000629 dl/kg/min per microU/ml
Standard Deviation 0.000193
|
SECONDARY outcome
Timeframe: Baseline and 12 weeksChange 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.
Outcome measures
| Measure |
GLP-1 Intervention
n=34 Participants
Participants will take a daily oral tablet of semaglutide for 4 months.
Semaglutide 3mg and 7mg \[Rybelsus\]: Once daily oral tablet of semaglutide for 4 months
|
Diet Intervention
n=17 Participants
Weight loss with dietary intervention
Weight loss diet: Prescribed weight loss diet to match weight loss in Drug arm
|
|---|---|---|
|
Change in Adipose Insulin Sensitivity
|
-1.431 percentage of change
Standard Deviation 9.97
|
0.44 percentage of change
Standard Deviation 12.06
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and 12 weeksThis outcome evaluates mitochondrial function and excess tricarboxylic acid (TCA) cycle substrate cycling by measuring indirect carbon contributions to newly synthesized triglycerides and glucose using stable isotope-labeled glycerol. Participants receive orally administered \[U-13C3\]glycerol mixed in water, and plasma glucose and lipids are analyzed by 13C NMR spectroscopy. Indirect glycerol carbon contribution reflects the fraction of glycerol carbons that first enter the TCA cycle before incorporation into triglycerides and glucose. A decrease in the percentage of indirect contributions is beneficial, indicating decreased oxidative stress resulting from excess TCA cycling.
Outcome measures
| Measure |
GLP-1 Intervention
n=34 Participants
Participants will take a daily oral tablet of semaglutide for 4 months.
Semaglutide 3mg and 7mg \[Rybelsus\]: Once daily oral tablet of semaglutide for 4 months
|
Diet Intervention
n=17 Participants
Weight loss with dietary intervention
Weight loss diet: Prescribed weight loss diet to match weight loss in Drug arm
|
|---|---|---|
|
Change in Percentage of Indirect Glycerol Carbon Contributions to Newly Synthesized Triglycerides and Glucose
|
3.08 percentage of indirect glycerol carbon c
Standard Deviation 5.24
|
-1.59 percentage of indirect glycerol carbon c
Standard Deviation 3.19
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and 12 weeksThe Free Androgen Index (FAI) is a test for hyperandrogenism in women, using testosterone and sex hormone binding globulin (SHBG) as markers. The calculation is FAI = Total Testosterone (nmol/ L)) x 100 / Sex Hormone-Binding Globulin (SHBG) (nmol/ L). Typical values for the FAI in women are 7-10, and FAI is usually elevated in women with PCOS. The change in FAI will be calculated after 12 weeks of diet or semaglutide intervention. A negative value means an improvement as there was a decrease in androgen levels after 12 weeks of treatment.
Outcome measures
| Measure |
GLP-1 Intervention
n=34 Participants
Participants will take a daily oral tablet of semaglutide for 4 months.
Semaglutide 3mg and 7mg \[Rybelsus\]: Once daily oral tablet of semaglutide for 4 months
|
Diet Intervention
n=17 Participants
Weight loss with dietary intervention
Weight loss diet: Prescribed weight loss diet to match weight loss in Drug arm
|
|---|---|---|
|
Change in Free Androgen Index
|
-2.45 unitless
Standard Deviation 3.27
|
-3.05 unitless
Standard Deviation 4.94
|
Adverse Events
Diet Intervention
GLP-1 Intervention
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Melanie Cree, MD, PhD
University of Colorado Anschutz Medical Campus
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place