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


OBJECTIVE
The objectives of this study were to monitor changes in IGF-I levels, glycemic control, and safety, particularly liver function and tumor size.


METHODS
This was a multicenter, open-label, 32-wk trial study.


METHODS
The study was performed at outpatient clinics.


METHODS
Fifty-three patients with acromegaly previously treated with octreotide long-acting release (LAR) participated in this study.


METHODS
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.


METHODS
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.
Barkan
Ariel L
AL
Department of Internal Medicine, University of Michigan Medical Center, 3920 Taubman Center, Ann Arbor, Michigan 48109-0354, USA. abarkan@med.umich.edu
Burman
Pia
P
Clemmons
David R
DR
Drake
William M
WM
Gagel
Robert F
RF
Harris
Philip E
PE
Trainer
Peter J
PJ
van der Lely
Aart Jan
AJ
Vance
Mary Lee
ML
D000172:Acromegaly / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D000236:Adenoma / Q000150:complications / Q000473:pathology; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D003692:Delayed-Action Preparations; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000150:complications
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D005947:Glucose; D006442:Glycated Hemoglobin; D019382:Human Growth Hormone; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D015282:Octreotide; C406545:pegvisomant