Preconception incretin therapy reduces pregnancy and cardiometabolic outcomes in polycystic ovary syndrome.
Abstract
Background
Polycystic ovary syndrome (PCOS), now polyendocrine metabolic ovarian syndrome (PMOS), is associated with reproductive and cardiometabolic complications. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonists (RAs) improve obesity-related outcomes, but their impact on pregnancy outcomes in PMOS remains unclear.
Methods
We conducted a target trial emulation using the TriNetX global federated health research network. Women ≥18 years with PCOS/PMOS receiving pre-conception GLP-1/dual GLP-1/GIP RA therapy (liraglutide, semaglutide or tirzepatide) were compared with metformin. Propensity score matching (1:1) accounted for demographics, anthropometrics, comorbidities and medications. The primary outcome was a composite of adverse pregnancy outcomes (hypertensive, glycaemic, placental, delivery, labour, foetal growth, preterm and early pregnancy complications) over two years. Individual pregnancy endpoints, major adverse cardiovascular events (MACE) and type 2 diabetes (T2D) were exploratory secondary outcomes. Cox regression generated hazard ratios (HRs) and 95% confidence intervals (CIs).
Results
After matching, 48,126 patients were included per group. Pre-conception GLP-1/GIP RA use was associated with lower risk of the composite pregnancy outcome (HR 0.38; 95% CI 0.34-0.41). Exploratory analyses also demonstrated lower risks of individual pregnancy endpoints, MACE (HR 0.88; 95% CI 0.81-0.95) and T2D (HR 0.31; 95% CI 0.30-0.33). Associations varied across some sensitivity analyses.
Conclusion
Pre-conception GLP-1/GIP RA use in women with PCOS/PMOS was associated with lower risks of adverse pregnancy outcomes and cardiometabolic disease compared with metformin, consistent with potential benefits of pre-conception metabolic optimisation. This study cannot evaluate in-pregnancy safety or efficacy, and these findings do not support GLP-1/GIP RA use during gestation.