Comparing the anorexigenic effects and mechanisms of gut-derived GLP-1 and its receptor agonists: insights into incretin-based therapies for obesity.

Obesity continues to increase worldwide. The primary cause of obesity is overeating, but the development of pharmacological treatments for obesity related to overeating has taken longer than expected. Recently, agonists of glucagon-like peptide-1 (GLP-1) receptor, designed based on the gut hormone GLP-1, have been developed as anti-obesity drugs and have demonstrated remarkable efficacy in treating both obesity and diabetes. Meanwhile, recent research using factors that promote GLP-1 secretion has highlighted the significance of endogenous GLP-1 function. This review provides an overview of the anorexigenic effects, adverse effects, and their underlying mechanisms of GLP-1 receptor agonists and endogenous gut-derived GLP-1. Furthermore, it discusses the potential anti-obesity effects of dual agonists targeting both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the GLP-1 receptor, which have gained attention in recent years. Finally, we compare the beneficial effects of GLP-1 receptor agonists and meal-induced gut GLP-1 secretion on overeating-induced obesity and discuss how combining these approaches may complement each other's limitations and serve as a promising long-term strategy for preventing and treating obesity.