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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