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These receptors exist on pancreatic beta cells (which produce insulin), brain regions controlling appetite and reward, the stomaComparing Mechanisms of Actionch and intestines, liver, heart, and other tissues

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In a systematic review by He et al., pooling data from 76 randomized controlled trials, it was observed that individuals receiving GLP-1RAs had a 37% higher relative risk of developing gallbladder disease compared with those not receiving them, with a marked increase in cases of cholelithiasis and cholecystitis

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Published by Cambridge University Press Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of glucose-lowering agents that are approved by the US Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM) and obesity, lowering the risk of major adverse cardiovascular events, as well as lowering the risk of worsening kidney disease, kidney failure, and death due to cardiovascular disease in adults with type 2 diabetes and chronic kidney disease.Reference Collins and Costello 1 GLP-1 RAs mimic the effects of endogenous GLP-1, which is an endocrine hormone produced in the L-cells of the intestine.Reference Zheng, Zong and Ma 2 Various metabolic effects have been associated with GLP-1, including stimulation of insulin secretion, inhibition of glucagon secretion, slowing gastric emptying, and increasing satiety.Reference Zheng, Zong and Ma 2 In addition to peripheral metabolic effects associated with GLP-1 RAs, extant literature reports GLP-1 RAs have effects within the central nervous system including improvements in cognitive and reward function, reducing the severity of the disparate domains of suicidality as well as protecting against neurodegeneration.Reference Au, Zheng and Le 3 Reference McIntyre, Rasgon and Goldberg 7 While the putative mechanism of action of GLP-1 RAs mainly focuses on agonism of the GLP-1 receptor, the downstream effects of GLP-1 receptor activation as well as potential off-target effects of GLP-1 RAs remain incompletely understood