Growth hormone receptor antagonists

Abstract

Pegvisomant is the first clinically available GHR antagonist. It prevents proper GHR dimerization and therefore inhibits GH action. In this review we have described the discovery and development of pegvisomant. We also reviewed the initial studies in animals and patients with active acromegaly or diabetic complications. In acromegaly, pegvisomant is the most effective treatment for normalizing IGF-I. With respect to long-term safety in acromegalic subjects, more data on tumor size and liver function during long-term treatment are needed. Preliminary results on the effects of GHR antagonists in animal models of diabetic nephropathy are encouraging. Additionally, the potential use of GHR antagonists for cancer indications is certainly exciting. However, it should be clearly stated that the efficacy of pegvisomant in diabetic patients and patients with cancer remains to be unequivocally established. Characterization of the potential benefit of pegvisomant for these indications is clearly an exciting arena.