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Key Points Animal studies suggest that endogenous, central glucagon-like peptide 1 (GLP-1) regulates both short-term and long-term energy balance, potentially via activation of hindbrain and hypothalamic GLP-1 receptors (GLP1R), respectively Endogenous peripheral GLP-1 may limit meal size by activation of GLP1R on local vagal afferent nerves and stimulation of a gutbrain feedback loop Increasing GLP1R activity by administering GLP-1 receptor agonists reduces food intake and promotes weight loss in humans, but the extent to which endogenous GLP-1 regulates energy balance in humans remains unknown Although diabetes mellitus and obesity appear to be associated with altered GLP-1 system activity, GLP1R agonists retain their efficacy in these contexts, making them a viable therapeutic tool A better understanding of how endogenous central and peripheral GLP-1 regulate energy balance has the potential to maximize our application of GLP-1-based therapies for the treatment of obesity This is a preview of subscription content, access via your institution Access options Subscribe to this journal Receive 12 print issues and online access 119.00 per year only 9.92 per issue Buy this article Purchase on SpringerLink Instant access to the full article PDF