Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant

Abstract

Context: In clinical practice, patients with acromegaly may be switched from therapy with long-acting somatostatin analogs to pegvisomant. The effect of changing therapies on glucose homeostasis and safety has not been reported. Objectives: The objectives of this study were to monitor changes in IGF-I levels, glycemic control, and safety, particularly liver function and tumor size. Design: This was a multicenter, open-label, 32-wk trial study. Setting: The study was performed at outpatient clinics. Patients: Fifty-three patients with acromegaly previously treated with octreotide long-acting release (LAR) participated in this study. Intervention: Pegvisomant (10 mg/d) was initiated 4 wk after the last dose of octreotide LAR and was adjusted based on serum IGF-I concentrations at wk 12, 20, and 28. Main Outcome Measures: The main outcome measures were changes in IGF-I, glycosylated hemoglobin A1c (HbA 1c), fasting plasma glucose, and safety during the first 12 wk after conversion. Results: At the end of pegvisomant treatment, IGF-I was normalized in 78% of patients. At wk 32, median fasting glucose concentration and HbA 1c were reduced (-1.4 mmol/liter and -0.4%, respectively; both P ≤ 0.0001) in the study population. Improvements in glycemic control occurred in patients with normal IGF-I concentrations at wk 4 [n = 15; fasting glucose, -1.7 mmol/liter (P ≤ 0.0001); HbA1c -0.2% (P = 0.03)]. Decreases in fasting glucose and HbA1c levels were observed in patients with and without diabetes. HbA1c was reduced by more than 1.0% in patients with diabetes. Median pituitary tumor volume did not change, although tumor volume increased in two patients with macroadenomas. Conclusions: Conversion from octreotide LAR to pegvisomant was safe and well tolerated. Improved glycemic control indicates that pegvisomant should be considered in patients with acromegaly and diabetes. Copyright © 2005 by The Endocrine Society.