New developments in GLP-1 agonist therapy for gestational diabetes: Systematic review on liraglutide, semaglutide, and exenatide from ClinicalTrials.gov

BACKGROUND: Gestational diabetes mellitus (GDM) is a widespread pregnancy complication, affecting approximately 7% to 10% of pregnancies worldwide and presenting risks for both maternal and fetal health. Traditional treatments, including lifestyle changes, insulin, and oral hypoglycemic agents, have limitations, particularly in terms of safety and potential fetal impacts. Glucagon-like peptide-1 (GLP-1) receptor agonists, initially developed for type 2 diabetes, have shown promise in managing GDM by improving glycemic control, enhancing insulin sensitivity, and assisting in weight management. However, safety and efficacy data in pregnancy remain limited. METHODS: A systematic review analyzed 8 clinical trials from ClinicalTrials.gov examining the use of GLP-1 liraglutide, semaglutide, and exenatide in GDM treatment. Studies varied in design, with the majority employing randomized, interventional protocols focusing on glycemic control and insulin sensitivity. Key outcome measures included hemoglobin A1c levels, glucose tolerance, insulin secretion, and progression to type 2 diabetes postpartum. RESULTS: GLP-1 receptor agonists effectively manage blood glucose and reduce pregnancy complications associated with GDM. However, side effects such as gastrointestinal discomfort and mild hypoglycemia were common, and all GLP-1 are categorized as pregnancy Category C by the U.S. Food and Drug Administration (FDA), with potential implications for fetal health due to transplacental passage. CONCLUSION: This review highlights the need for large-scale, long-term studies to establish standardized protocols and assess the safety and efficacy of GLP-1 in managing GDM, potentially expanding therapeutic options for this condition.