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Retatrutide (LY3437943): Educational Overview Executive Summary Retatrutide is an investigational triple-agonist incretin therapy activating: GLP-1 receptors GIP receptors glucagon receptors This multi-pathway engagement affects: appetite regulation insulin signaling lipid metabolism hepatic glucose handling energy expenditure References: Coskun T et al., Cell Metabolism , 2022 Jastreboff AM et al., NEJM , 2023 Mechanism of Action GLP-1 Receptor Activation GLP-1 signaling: increases glucose-dependent insulin secretion slows gastric emptying activates satiety pathways in the brain Reference: Drucker DJ, Cell Metabolism , 2018 GIP Receptor Activation GIP signaling: enhances insulin secretion improves adipocyte insulin sensitivity modulates lipid metabolism References: Finan B et al., Nature Medicine , 2013 Nauck MA et al., Diabetes Care , 2021 Glucagon Receptor Activation Retatrutide uniquely activates glucagon receptors

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