MON-189 Comparative Effectiveness of GLP-1 Analogues and Metformin in Managing Polycystic Ovarian Syndrome: Insights from a Propensity-Matched Cohort Study

Abstract Disclosure: M.J. Barnett: None. J.R. Lam: None. C. Casipit: None. A. Rivadeneira: None. Introduction: Polycystic Ovarian Syndrome (PCOS) is a multifaceted condition affecting reproductive, metabolic, and psychological health. This study compares the effectiveness of Glucagon-like peptide-1 (GLP-1) analogues versus Metformin in managing PCOS among women aged 18-45 years with a Body Mass Index (BMI) ≥25 kg/m². Objective: To evaluate and compare reproductive, metabolic, and psychological outcomes in PCOS patients treated with GLP-1 analogues versus Metformin, focusing on pregnancy, endocrine, and mental health parameters. Methods: This retrospective cohort study utilized data from the TriNetX Global Collaborative Network, encompassing 143 healthcare organizations. The GLP-1 cohort included 9,574 patients, and the Metformin cohort included 61,642 patients, balanced using propensity score matching (final n = 9,572 per cohort). Cohorts were defined by PCOS diagnosis, BMI ≥25 kg/m², and exclusion of prior treatment with the comparator medication. Outcomes included reproductive events (pregnancy, delivery, preeclampsia), endocrine changes (luteinizing hormone [LH], follicle-stimulating hormone [FSH], androgen levels), and mental health diagnoses. A 3-year observation period was analyzed using risk ratios and standardized mean differences, excluding patients with pre-existing conditions affecting outcomes. Results: The cohorts were demographically similar after matching (mean age 34 years, predominantly White). Exclusions due to prior outcomes were 2,309 (24%) in GLP-1 and 2,278 (24%) in Metformin for pregnancy-related outcomes. Pregnancy incidence was higher in the Metformin cohort (10.7% vs. 3.2%, p < 0.001), and delivery (Vaginal and Cesarean) (4.9% vs. 0.7%, p < 0.001). GLP-1 treatment showed lower risks for amenorrhea (RR = 0.311, p < 0.001), preeclampsia (RR = 0.246, p < 0.001), and mental health disorders (Anxiety and Depression) (RR = 0.770, p < 0.001). Metabolic outcomes favored GLP-1, with reduced Dehydroepiandrosterone sulfate (DHEAS) levels (mean = 198.5 µg/dL vs. 220.8 µg/dL, p = 0.003) and a non-significant improvement in LH values (8.7 vs. 9.6 IU/L, p = 0.199). FSH levels were significantly higher in the GLP-1 cohort (7.3 vs. 6.3 IU/L, p = 0.033). Conclusion: GLP-1 analogues excel in metabolic regulation and menstrual regularity, while Metformin enhances fertility outcomes. Individualized treatment plans should leverage these complementary profiles to optimize PCOS management. Presentation: Monday, July 14, 2025