In women with PCOS and obesity, liraglutide beat metformin at improving metabolism, hormone levels, and natural pregnancy rates — possibly by altering leptin gene expression in ovarian cells.
Higher natural pregnancy rateWomen with PCOS and obesity on liraglutide achieved significantly more natural pregnancies than those on metformin (p<0.05)
What the researchers found
Liraglutide (a GLP-1 receptor agonist) outperformed metformin across multiple endpoints in women with PCOS and obesity. Compared to metformin, liraglutide produced greater improvements in glucose metabolism, lipid metabolism, BMI, leptin levels, and reproductive hormone levels (FSH, E2, LH) — all statistically significant (p<0.05).
Critically, liraglutide reduced methylation of the leptin promoter in ovarian granulosa cells more than metformin. The liraglutide group also had higher rates of menstrual cycle restoration, normal ovulation, and natural pregnancy compared to the metformin group.
Why it matters
PCOS is the most common cause of infertility in women, and obesity worsens it. This study suggests liraglutide may improve fertility outcomes through an epigenetic mechanism — changing how the leptin gene is expressed in ovarian cells — offering a new angle on why GLP-1 drugs might help women with PCOS conceive naturally.
The numbers in context
n=30 · 15 per group · p<0.05 for all comparisons · Liraglutide group had higher ovulation and pregnancy rates vs metformin
How the study worked
Retrospective analysis of 30 women with PCOS and obesity, randomly divided into two groups of 15. The control group received metformin; the observation group received subcutaneous liraglutide injections. Researchers compared glucose/lipid metabolism markers, BMI, hormones (FSH, E2, LH), leptin promoter methylation in ovarian granulosa cells, and reproductive outcomes (menstrual regularity, ovulation, natural pregnancy).
Who was studied
30 women with polycystic ovary syndrome (PCOS) and obesity
What this study cannot tell us
Very small sample size (15 per group) severely limits statistical power and generalizability. The study is described as retrospective yet uses random grouping, which is methodologically unclear. No specific dosing or duration details are provided in the abstract. The mechanism linking leptin promoter methylation to fertility outcomes is proposed but not conclusively demonstrated.
How to read the evidence
This is a small retrospective study with only 30 patients (15 per group). While the results are statistically significant, the small sample size, unclear methodology (retrospective but randomized), and single-center design limit confidence in the findings.
When this study was published
Published in 2025, this is a recent study reflecting growing interest in GLP-1 drugs for PCOS and fertility applications.
The bigger picture
GLP-1 drugs are increasingly studied for PCOS beyond their weight loss effects. This study adds an epigenetic dimension — suggesting liraglutide may directly influence gene expression in ovarian cells, not just improve fertility indirectly through weight loss and metabolic improvement. If confirmed in larger studies, this could reshape how we think about GLP-1 drugs for reproductive health.
Questions still open
- Would newer GLP-1 drugs like semaglutide or tirzepatide show even stronger effects on ovarian leptin methylation and fertility?
- Is the fertility improvement driven primarily by the epigenetic changes in ovarian cells, or is it mostly a downstream effect of weight loss and metabolic improvement?
- How long do the epigenetic changes in granulosa cells persist after stopping liraglutide treatment?
Common questions
How might a GLP-1 drug like liraglutide help with PCOS fertility?
Is liraglutide approved for treating PCOS?
Read the original research
Effects of Liraglutide on Leptin Promoter Methylation in Ovarian Granulosa Cells of Patients with Polycystic Ovary Syndrome and Obesity.
Gynecologic and obstetric investigation, 90(1), 6-17
Citation
Zhao, Hongli; Guo, Yanying. (2025). Effects of Liraglutide on Leptin Promoter Methylation in Ovarian Granulosa Cells of Patients with Polycystic Ovary Syndrome and Obesity.. Gynecologic and obstetric investigation, 90(1), 6-17. https://doi.org/10.1159/000539039