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Its signaling complexity (triple agonism) imposes heightened methodological vigilance: systematic glycemic monitoring to detect any paradoxical hyperglycemia linked to the glucagon arm, regular hepatic panel given the lipolytic effect, and lean mass tracking to quantify the share of weight loss linked to muscle depletion under severe caloric restriction

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Under conditions of reduced caloric intake, AMPK-mediated suppression of anabolic pathways, combined with diminished amino acid availability, may constrain mechanistic target of rapamycin (mTOR) signaling and translational capacity [52, 88]