A safety review of approved oral agents for treating type 2 diabetes and associated diseases in pregnant patients.

[INTRODUCTION] Hyperglycemia in pregnancy, including gestational diabetes mellitus (GDM) and pregestational diabetes, significantly impacts maternal and neonatal outcomes, necessitating effective management strategies. Insulin is the first-line therapy; however, adherence barriers, cost, and route of administration challenges have driven interest in oral agents like metformin and glyburide. These agents offer practical alternatives but raise questions about long-term safety and fetal exposure.

[AREAS COVERED] This review evaluates the pharmacokinetics, pharmacodynamics, and clinical outcomes of metformin and glyburide, focusing on their roles in GDM, pregestational diabetes, polycystic ovary syndrome (PCOS), and obesity. Maternal outcomes, neonatal impacts, and long-term offspring health were assessed to determine the safety of these therapies.

[EXPERT OPINION] Metformin reduces insulin dependency and weight gain during pregnancy but raises concerns about short and long-term offspring impacts, such as increased SGA rates (22% vs. 5%), altered growth patterns, and offspring neurocognition. Glyburide is effective for glycemic control but carries higher neonatal hypoglycemia risks and lacks robust long-term safety data. Both agents hold promise as alternatives to insulin, particularly in resource-limited settings. However, further research is needed to address knowledge gaps, optimize their use, and ensure safe integration into clinical practice.