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Compared to peptide GLP- 1 receptor agonists, orforglipron, exhibits less receptor desensitization by increasing cyclic AMP signaling [105]

When that signal is removed, there's a period of readjustment where the orexigenic circuits are overcompensating

Aqueous solubility affects absorption, formulation and ability of a compound to be delivered in sufficient concentrations to be active, and even in vitro activity