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Metabolic Adaptation (Your Body Fights Back) After several weeks in a caloric deficit, your body makes adjustments: Resting metabolic rate drops the body reduces energy expenditure to defend its fat stores Adaptive thermogenesis non-exercise activity (fidgeting, posture, unconscious movement) decreases Leptin levels fall as fat mass drops, leptin (the satiety signal) decreases, which can increase hunger at the margin Retatrutide's triple agonism (GLP-1, GIP, glucagon) helps counter this better than semaglutide or tirzepatide alone the glucagon component specifically boosts resting metabolic rate and fat oxidation