Trial results for semaglutide (oral formulations 3mg and 7mg, Rybelsus) in adolescent girls with PCOS, obesity, and NAFLD were posted on ClinicalTrials.gov on 2025-11-25. The study showed that the GLP-1 Intervention group achieved a mean weight reduction of -5.30 kg, compared to -1.66 kg for the Diet Intervention group.
Background
The trial investigated semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, as a potential treatment for adolescent girls with polycystic ovarian syndrome (PCOS), obesity, and non-alcoholic fatty liver disease (NAFLD). The study aimed to decrease metabolic syndrome, lower hepatic fat, and improve insulin sensitivity over a 12-week period.
Trial design
The study (NCT03919929) was a Phase 2/3, randomized trial that enrolled 60 participants. It investigated oral semaglutide (Rybelsus 3mg and 7mg) in adolescent girls with PCOS, obesity, and NAFLD. Participants were assigned to either a GLP-1 Intervention group or a Diet Intervention group (active lifestyle intervention).
Key results
The trial results showed differences between the GLP-1 Intervention and Diet Intervention groups across several metabolic parameters:
- For "Change in Weight":
- The GLP-1 Intervention group showed a mean change of -5.30 kg (Standard Deviation: 4.92).
- The Diet Intervention group showed a mean change of -1.66 kg (Standard Deviation: 2.81).
- For "Change in Rate of De Novo Lipogenesis (DNL)":
- The GLP-1 Intervention group showed a mean change of -1.9 mg/dL (Standard Deviation: 1.0).
- The Diet Intervention group showed a mean change of 0.94 mg/dL (Standard Deviation: 5.7).
- For "Change in Hepatic Fat Fraction":
- The GLP-1 Intervention group showed a mean change of -1.84 Change in percentage of liver fat (Standard Deviation: 4.39).
- The Diet Intervention group showed a mean change of -1.41 Change in percentage of liver fat (Standard Deviation: 2.24).
- For "Change in Whole Body Insulin Sensitivity":
- The GLP-1 Intervention group showed a mean change of 0.000213 dl/kg/min per microU/ml (Standard Deviation: 0.000423).
- The Diet Intervention group showed a mean change of 0.0000629 dl/kg/min per microU/ml (Standard Deviation: 0.000193).
- For "Change in Adipose Insulin Sensitivity":
- The GLP-1 Intervention group showed a mean change of -1.431 percentage of change (Standard Deviation: 9.97).
- The Diet Intervention group showed a mean change of 0.44 percentage of change (Standard Deviation: 12.06).
- For "Change in Percentage of Indirect Glycerol Carbon Contributions to Newly Synthesized Triglycerides and Glucose":
- The GLP-1 Intervention group showed a mean change of 3.08 percentage of indirect glycerol carbon c (Standard Deviation: 5.24).
- The Diet Intervention group showed a mean change of -1.59 percentage of indirect glycerol carbon c (Standard Deviation: 3.19).
What this means
The results suggest that oral semaglutide may offer a more pronounced benefit in weight reduction and in decreasing the rate of de novo lipogenesis compared to an active lifestyle intervention in adolescent girls with PCOS, obesity, and NAFLD. These findings indicate a potential role for semaglutide in managing the metabolic complications associated with these conditions in this specific patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03919929, titled 'Treating PCOS With Semaglutide vs Active Lifestyle Intervention,' were posted on 2025-11-25 on clinicaltrials.gov.