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.

Keywords: glucagon‐like peptide‐1 receptor agonists; periconceptional exposure; pregnancy outcomes; type 2 diabetes mellitus.