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Comparing the Effects of Glucagon-Like Peptide-1 Receptor Agonists on Cardiovascular Events to Metformin in Patients With Polycystic Ovary Syndrome: A Real-World Multicenter Cohort Study Across the United States [ID 1078]

Tina Yi Jin Hsieh, Ting-Wei-Er-Nie Liao, Sheng-Yin Chen, Chuan Lu, Gin-Yi Lee

Obstetrics & Gynecology, 2025

Abstract

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP1RA), known for their weight-loss and antidiabetic effects, have been recommended by the American Diabetes Association as a first-line treatment for type 2 diabetes mellitus due to their cardiovascular benefits. However, the effects of GLP1RA on polycystic ovary syndrome (PCOS) remain unclear. The study aims to compare the effects of GLP1RA on cardiovascular events in PCOS to metformin, an active comparator with known cardiometabolic benefits. METHODS: We included females aged 12 or older who were diagnosed with PCOS and had at least two prescriptions of GLP1RA or metformin from May 1, 2005 (first GLP1RA approval), to December 31, 2021, from the TriNetX database with 60 or more U.S. health care institutions. After 1:1 propensity score matching on body mass index, comorbidities, lipid profiles, Hb A1C, and medications, hazard ratios (HRs) and 95% CIs for outcomes were calculated using the Cox regression model. Patients were observed for 3 years after drug initiation and censored if: 1) cardiovascular event diagnosis; 2) study end date: May 17, 2024; 3) loss to follow-up, whichever occurred first. RESULTS: Compared to metformin, GLP1RA was associated with significantly reduced arrhythmia (HR 0.83; 95% CI, 0.75–0.91) and thrombotic disorders (HR 0.78; 95% CI, 0.68–0.90). GLP1RA was associated with a lower, although nonsignificant, risk of cerebrovascular events (HR 0.88; 95% CI, 0.77–1.01), inflammatory heart disease…

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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.

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