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(Endocrinology, 2010), demonstrated a strong species-dependent effect: In rodents: High GLP-1 receptor expression in thyroid C-cells Strong cAMP signaling activation Persistent stimulation leads to tumor formation In humans and primates: Minimal or absent functional GLP-1 receptor expression in C-cells No meaningful calcitonin elevation under therapeutic exposure No observed C-cell proliferation in long-term studies Even exposure levels far exceeding clinical doses failed to reproduce rodent-like thyroid effects in primate models

doi: 10.1210/jc.2014-2547 26 HelstedMMGasbjergLSLanngARBergmannNCStensenSHartmannBet al

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