Unintentional periconceptional exposure to glucagon‐like peptide‐1 receptor agonists and adverse pregnancy outcomes: A nationwide cohort study in Taiwan

Abstract Aims To assess whether periconceptional exposure to glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) is associated with adverse outcomes in women with pregestational type 2 diabetes. Materials and Methods We linked Taiwan's Birth Certificate Application and National Health Insurance claims (2013–2022) to assemble a nationwide cohort of singleton births to mothers (18–50 years) with pregestational diabetes. Exposure was any GLP‐1 RA dispensed during the 90 days before and after the last menstrual period; insulin without GLP‐1 RA was the active comparator. Outcomes were major congenital malformations, stillbirth, preterm birth (<37 weeks) and small for gestational age (SGA, <10th percentile). We used 1:4 propensity‐score matching and Poisson generalised estimating equation (GEE); sensitivity analyses required ≥2 prescriptions and restricted exposure to the first trimester. Results We identified 3351 comparison pregnancies (GLP‐1 RA 160; insulin 3191); matching yielded 160 versus 606. Risk ratios (GLP‐1 RA vs. insulin) were malformations 0.64 (95% confidence interval 0.11–3.83), stillbirth 2.05 (0.82–5.13), preterm birth 1.09 (0.85–1.39) and SGA 0.86 (0.31–2.41). Sensitivity analyses were similar. Conclusions Periconceptional GLP‐1 RA exposure was not associated with increased risks of malformations, stillbirth, preterm birth or SGA versus insulin use. These preliminary data require confirmation in larger agent‐specific studies; until then, intentional GLP‐1 RA use in planned pregnancy is not advised.