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Furthermore, most patients who start treatment with GLP-1RA for obesity discontinue treatment within 1 year because of side effects, high cost, or reaching a plateau in weight loss [106]
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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 gut–brain 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 Review criteria
