Glucagon-Like Peptide-1 Receptor Agonists in Inflammatory Bowel Disease: From Metabolic Regulation to Immunomodulation Along the Gut–Immune–Metabolic Axis

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the treatment of type 2 diabetes mellitus and obesity through potent metabolic and cardiometabolic effects. Beyond glucose regulation, accumulating evidence indicates that GLP-1 signalling exerts pleiotropic actions on intestinal physiology, epithelial barrier integrity, mucosal immunity and host–microbiota interactions, suggesting a potential therapeutic role in inflammatory bowel disease (IBD). Concurrently, the increasing prevalence of obesity and metabolic dysfunction among patients with IBD has highlighted the need for therapeutic approaches that address both intestinal inflammation and its metabolic determinants. This review summarizes the physiological functions of GLP-1 and critically evaluates the molecular, experimental and clinical evidence concerning GLP-1 receptor agonists in IBD. Particular emphasis is placed on epithelial barrier function, innate and adaptive immunity, inflammatory signalling, intestinal permeability and gut microbial homeostasis. Experimental studies generally support anti-inflammatory and mucosal-protective effects in preclinical models, whereas emerging clinical evidence indicates substantial metabolic efficacy and generally reassuring short-term safety. A central concept of this review is the gut–immune–metabolic axis, integrating endocrine signalling, epithelial function, mucosal immunity, gut microbiota and systemic metabolism. Nevertheless, adequately powered prospective randomized controlled trials with objective inflammatory, endoscopic and histological endpoints are required before GLP-1RAs can be considered disease-modifying therapies in IBD.