Prolonged Semaglutide Treatment Reveals Stage-Dependent Changes to Feeding Behavior and Metabolic Adaptations in Male Mice

Although many studies have demonstrated acute behavioral and metabolic effects of glucagon-like peptide 1 receptor (GLP-1R) agonists, few have assessed long-term effects of these drugs on these phenotypes. We assessed changes in various behavioral and metabolic phenotypes throughout a 21-day treatment regimen with semaglutide and posttreatment. Weight loss in response to prolonged semaglutide treatment can be divided into distinct phases, and each phase is characterized by different effects on food intake, meal patterns, energy expenditure, and substrate oxidation. Our findings suggest that differences in behavioral changes and/or metabolic adaptations may underlie the degree of weight loss responsiveness to GLP-1R agonists.