Abstract Body: Introduction: Polycystic ovary syndrome is strongly associated with insulin resistance, obesity, and adverse cardiometabolic risk. Metformin is commonly used in patients with polycystic ovary syndrome and metabolic risk factors, but comparative real-world evidence evaluating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus metformin for cardiometabolic outcomes remains limited.
Hypothesis: We assessed the hypothesis that initiation of GLP-1 RAs, compared with metformin, is associated with a lower risk of adverse cardiometabolic outcomes in women with polycystic ovary syndrome.
Methods: We performed a retrospective cohort study using the TriNetX United States database from 2004 to 2024. Adult women with a diagnosis of polycystic ovary syndrome who initiated either a GLP-1 RA or metformin after diagnosis were identified and followed for 1 year from treatment initiation. Cohorts were propensity score-matched 1:1 for demographics and baseline endocrine and cardiovascular comorbidities. Primary outcomes were incident hypertension, incident diabetes mellitus, acute myocardial infarction, and all-cause mortality. After matching, the study included 25,225 patients in each group.
Results: Compared with metformin, GLP-1 RA use was associated with a significantly lower 1-year risk of incident diabetes mellitus (relative risk 0.458, 95% confidence interval 0.414–0.507; p<0.0001) and all-cause mortality (relative risk 0.364, 95% confidence interval 0.218–0.606; p<0.0001).
Conclusions: In conclusion, among women with polycystic ovary syndrome in a large propensity score-matched real-world cohort, initiation of GLP-1 RAs was associated with lower 1-year risks of incident diabetes mellitus and all-cause mortality compared with metformin. These findings support further prospective studies evaluating glucagon-like peptide-1 receptor agonists as a cardiometabolic risk-modifying strategy in polycystic ovary syndrome.