Mechanism of action of pegvisomant

Mechanism of action of pegvisomant

Pegvisomant is a human GH receptor antagonist that competes with endogenous GH for binding to its receptor and blocks production of IGF-1. This improves the clinical effects and metabolic defects in acromegaly. Pegvisomant controls IGF-1 levels in about two thirds of patients. It does not appear to affect tumor size in the great majority of patients, but tumor size should be monitored, given the drug’s mechanism of action. It is usually used in patients who are resistant to or do not tolerate somatostatin analogues, or in combination with somatostatin analogues to improve biochemical control. The main side effect of pegvisomant is liver function abnormalities, which are usually transient. Note that IGF-1 remains an accurate biomarker for acromegaly control in pegvisomant-treated patients, but GH levels cannot be monitored because of the persistence of GH hypersecretion.


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