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We demonstrate that two peptide biased agonists (GEP44 and GEP12) of the GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors (GLP-1R, Y1-R, and Y2-R, respectively) elicit Y1-R antagonist-controlled, GLP-1R-dependent stimulation of insulin secretion in both rat and human pancreatic islets, thus revealing the counteracting effects of Y1-R and GLP-1R agonism

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Tirzepatide (Mounjaro, Zepbound) is a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, though these medications are often collectively referred to as incretin-based therapies

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