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

J Clin Endocrinol Metab. 2005 Oct;90(10):5684-91. doi: 10.1210/jc.2005-0331. Epub 2005 Aug 2.

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 (HbA1c), 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 HbA1c were reduced (-1.4 mmol/liter and -0.4%, respectively; both P < or = 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 < or = 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acromegaly / blood*
  • Acromegaly / drug therapy*
  • Acromegaly / etiology
  • Adenoma / complications
  • Adenoma / pathology
  • Adolescent
  • Adult
  • Area Under Curve
  • Blood Glucose / metabolism
  • Delayed-Action Preparations
  • Female
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Glycated Hemoglobin / metabolism
  • Homeostasis / drug effects*
  • Human Growth Hormone / administration & dosage
  • Human Growth Hormone / adverse effects
  • Human Growth Hormone / analogs & derivatives*
  • Human Growth Hormone / blood
  • Human Growth Hormone / therapeutic use
  • Humans
  • Insulin / blood
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Middle Aged
  • Octreotide / administration & dosage
  • Octreotide / adverse effects*
  • Octreotide / therapeutic use*
  • Pituitary Neoplasms / complications

Substances

  • Blood Glucose
  • Delayed-Action Preparations
  • Glycated Hemoglobin A
  • Insulin
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Glucose
  • pegvisomant
  • Octreotide