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The fact that the double-cysteine mutations only partially abolish the physiological function may imply that not all the expressed mutants have an intact disulfide bridge and that the observed conformation is only one possible inactive state on the cell surface, as supported by the EM data and MD simulations below
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In November 2024, the SUMMIT trial was published, examining the use of tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and GLP1 receptors, in 731 patients with obesity and HFpEF
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