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Here, the authors report cryo-EM structures of tirzepatide-bound GIPR and GLP-1R, peptide 20-bound GIPR, GLP-1R and GCGR, revealing the molecular basis of their multiplexed pharmacological actions.

The use of GLP-1RA is a new therapeutic strategy that addresses both metabolic and cognitive/neuropsychiatric aspects, which is fundamentally important for the treatment of comorbid diseases.

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However, because glucagon-like peptide-1 receptor agonists work to slow gastric emptying, a safety concern has been raised in patients undergoing deep sedation or general anesthesia regarding gastric aspiration, and considering their long half-life in the blood, they are difficult to manage in the perioperative period

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