Preconception incretin therapy associated with fewer adverse pregnancy outcomes in PCOS

A target trial emulation using the TriNetX global health research network examined whether preconception incretin therapy was associated with pregnancy and cardiometabolic outcomes in women aged 18 years or older with polycystic ovary syndrome (PCOS). Investigators compared liraglutide, semaglutide or tirzepatide with metformin, matching patients for demographics, anthropometrics, comorbidities and medications. The primary endpoint was a composite of adverse pregnancy outcomes over two years.

After propensity score matching, each group included 48,126 patients. Preconception incretin use was associated with a lower hazard of the composite pregnancy endpoint (hazard ratio [HR] 0.38; 95% CI 0.34–0.41), which encompassed hypertensive, glycaemic, placental, delivery, labour, foetal growth, preterm and early pregnancy complications. Exploratory analyses also found lower hazards of major adverse cardiovascular events (HR 0.88; 95% CI 0.81–0.95) and type 2 diabetes (HR 0.31; 95% CI 0.30–0.33), alongside lower risks of individual pregnancy endpoints.

The findings suggest potential benefits of preconception metabolic optimisation, but the observational design cannot establish causality. Associations varied across some sensitivity analyses, and absolute event rates were not provided in the available abstract. Crucially, the study cannot assess safety or efficacy during pregnancy and does not support GLP-1/GIP receptor agonist use during gestation.