A Comparison of the Effects of Pegvisomant and Octreotide on Glucose, Insulin, Gastrin, Cholecystokinin, and Pancreatic Polypeptide Responses to Oral Glucose and a Standard Mixed Meal

摘要: Standard medical therapy for patients with acromegaly includes somatostatin analogs. Owing to the widespread expression of receptors, these may be associated unwanted effects, such as altered glucose tolerance and impaired gut hormone release. Pegvisomant is a novel pegylated GH analog that competes wild-type GH-receptor binding sites but contains position 120, amino acid substitution prevents functional receptor dimerization, known prerequisite signal transduction generation IGF-I. We have studied short-term effects two therapies (pegvisomant 20 mg/d 7 d octreotide 50 microg thrice daily d) on stimulated release in six healthy male volunteers an open-label, random-order, cross-over study. Subjects were assessed at baseline (oral test standard mixed meal) 6 each minimum washout 2 wk between treatments. Area under curve peak responses analyzed using one-way repeated-measures ANOVA (on ranks where appropriate). had no effect or response during oral meal. In contrast, significantly increased fasting plasma glucose, lowered insulin, led deterioration tolerance; three subjects developed one diabetes mellitus by World Health Organization criteria. Octreotide cholecystokinin, gastrin, pancreatic polypeptide. conclusion, pegvisomant, unlike octreotide, not impairment normal males.