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GLP-1R-mediated effects include [8]: Glucose-dependent insulin secretion (complementary to GIP pathway) Glucagon suppression during hyperglycemia Delayed gastric emptying Central appetite suppression via hypothalamic and brainstem circuits Synergistic Mechanisms The dual agonism of tirzepatide produces several synergies that explain its superior efficacy: Complementary appetite suppression : GIP and GLP-1 receptors are expressed on distinct neuronal populations in the hypothalamus