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Quick Answer: GLP-1 receptor agonist-related fatigue likely results from multiple indirect mechanisms including substantial caloric restriction, gastrointestinal side effects causing dehydration and nutritional deficits, and metabolic adaptation during weight loss, rather than a single direct pharmacological effect

Specifically, the extracellular half of TM7 in GCGR shifts outward by 4.56 and 3.02 (measured by the C of R 7.35b , class B1 GPCR numbering in superscript 12 ), facilitating the outward orientation of retatrutides N-terminus by 2.84 and 2.61 (measured by the C of Y1 P , P in superscript indicates peptide residue) compared to these residues at retatrutideGLP-1R and retatrutideGIPR structures, respectively