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The multiple conformations observed from the single-particle EM analysis of the purified Fab7F38semaglutideGLP-1RGsNb35 complex most likely represent different agonist-bound ECD conformations, however some 2D classes are also compatible with the closed conformation observed in our inactive crystal structure (Supplementary Fig
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In doing so, we advocate for a paradigm that moves beyond traditional indications, embracing the full spectrum of GLP-1R agonists in areas such as primary prevention, microvascular protection, and metabolic liver disease, and metabolic disorders that include cardio-kidney-metabolic (CKM) syndromea systemic disorder characterized by interrelated metabolic, renal, and cardiovascular dysfunction and a broader cardio-renal-metabolic axis that includes central obesity, insulin resistance, dyslipidemia, hypertension, and pre-diabetic states
