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Glucagon-like peptide-1 (GLP-1) receptor agonists were touted as breakthrough drugsin 2023 and their popularity has soared since. More than 4 million items of tirzepatide and semaglutide were dispensed on the NHS in England in 2025/20261, while around2.5 million people each monthaccessed GLP-1s privately at the end of 2025, according to James Kingsland, chair of []

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Here, we report three cryo-electron microscopy structures of GLP-1R bound to (i) compound 2 (an ago-allosteric modulator)

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