Abstract
BACKGROUND AND AIMS: Vascular dysfunction, driven by endothelial impairment, arterial stiffness, inflammation, and immune activation, contributes to cardiometabolic disorders such as hypertension and atherosclerosis. Sex differences and sex hormones influence the progression of vascular and immune dysfunction. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), regulate glucose homeostasis and also impact vascular and immuno-metabolic health. This review examines their roles in these processes, with emphasis on sex-specific effects. METHODS: A narrative review of preclinical and clinical studies assessing GLP-1 and GIP actions on vascular function, immune regulation, and metabolism, and their modulation by sex and sex hormones. RESULTS: Incretins improve endothelial function, reduce vascular inflammation, and modulate immune-metabolic crosstalk, processes often impaired in cardiometabolic disease. Sex differences affect incretin secretion, signalling, and therapeutic responses, though underlying mechanisms remain unclear. CONCLUSIONS: Incretin hormones are promising targets for improving vascular and immune-metabolic health in cardiometabolic disorders. Understanding sex-specific mechanisms will be essential for optimizing incretin-based therapies.