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Glucose Homeostasis and Safety in Patients with Acromegaly Converted from Long-Acting Octreotide to Pegvisomant

Departments of Internal Medicine and Neurosurgery (A.L.B.), University of Michigan Medical Center, Ann Arbor, Michigan 48109-0354; Pfizer, Inc. (P.B., P.E.H.), New York, New York 10017-5755; Division of Endocrinology/Metabolism, University of North Carolina School of Medicine (D.R.C.), Chapel Hill, North Carolina 27599; Department of Endocrinology, St. Bartholomew’s Hospital (W.M.D.), London EC1A 7BE, United Kingdom; Department of Endocrinology (W.M.D., P.J.T.), Christie Hospital, Manchester M20 4BX, United Kingdom; Division of Internal Medicine, University of Texas M. D. Anderson Medical Center (R.F.G.), Houston, Texas 77030; Erasmus Medical Center Rotterdam (A.J.v.d.L.), 3000 CA Rotterdam, The Netherlands; and Department of Internal Medicine, University of Virginia Health Sciences Center (M.L.V.), Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Dr. Ariel L. Barkan, Departments of Internal Medicine and Neurosurgery, University of Michigan Medical Center, 3920 Taubman Center, Ann Arbor, Michigan 48109-0354. E-mail: abarkan{at}med.umich.edu.

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 A_1c (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); HbA_1c –0.2% (P = 0.03)]. Decreases in fasting glucose and HbA_1c levels were observed in patients with and without diabetes. HbA_1c 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.

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