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Zhang, Y., et al., Glucagon Potentiates Insulin Secretion Via beta-Cell GCGR at Physiological Concentrations of Glucose

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Yassin et al., 2025

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The mechanistic interpretation, debated for two decades, was that GIPR agonism did two things: it contributed to appetite suppression and energy expenditure in addition to GLP-1R activation, and - separately - it appeared to improve tolerability by reducing GLP-1-mediated nausea and GI adverse events