Treatment of Gestational Diabetes: Molecular Transport Mechanisms, Shear Stress Adaptation, and Efficacy Comparison Between Liraglutide and Insulin

Abstract Gestational diabetes mellitus (GDM) involves maternal hyperglycemia, dyslipidemia, and inflammation, impairing placental function through overexpression of nutrient transporters and altered vascular responses. These changes contribute to fetal overgrowth, hyperinsulinemia, and long-term metabolic risks. Therapies like insulin and glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide) aim to restore metabolic and vascular balance in GDM pregnancies. To compare insulin and liraglutide in GDM management, focusing on placental molecular transport regulation, endothelial shear stress adaptation, and efficacy in restoring placental function and fetal nutrient balance. A comparative literature review was conducted using peer-reviewed studies on insulin and liraglutide therapy in GDM. Key molecular pathways were analyzed, including glucose transporter type 1 (GLUT1)-mediated glucose transport, mechanistic (mammalian) target of rapamycin (mTOR)-regulated lipid and amino acid transport, and amp-activated protein kinase (AMPK)/endothelial nitric oxide synthase (eNOS)-related endothelial function. Human clinical data and experimental model findings were assessed to evaluate changes in placental transporter expression, maternal lipid profiles, inflammatory markers, and uteroplacental blood flow. Both therapies reduce maternal hyperglycemia and downregulate GLUT1, limiting fetal glucose excess. Insulin improves placental lipid handling by reducing maternal lipotoxicity. Liraglutide, though not approved for GDM, enhances insulin sensitivity, lowers triglycerides and free fatty acids, and reduces inflammation in experimental settings. It activates AMPK/eNOS signaling, improving endothelial function and placental perfusion, and alleviates endoplasmic reticulum (ER) stress, helping restore transporter regulation under hyperglycemia. Insulin remains the standard GDM treatment by correcting insulin deficiency. Liraglutide shows promise due to its broader metabolic and vascular benefits, but requires further research to confirm its safety and efficacy in pregnancy.