The Impact of Pegvisomant Treatment on Substrate Metabolism and Insulin Sensitivity in Patients with Acromegaly

• Published in: The journal of clinical endocrinology and metabolism Vol. 92; no. 5; pp. 1724 - 1728
• Main Authors: Lindberg-Larsen, Rune, Møller, Niels, Schmitz, Ole, Nielsen, Søren, Andersen, Marianne, Ørskov, Hans, Jørgensen, Jens O. L.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-05-2007
• Subjects: Acromegaly - drug therapy; Acromegaly - metabolism; Biological and medical sciences; Blood Glucose - metabolism; Body Composition - drug effects; Calorimetry, Indirect; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Glucose Clamp Technique; Glucose Tolerance Test; Human Growth Hormone - analogs & derivatives; Human Growth Hormone - therapeutic use; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Insulin Resistance - physiology; Insulin-Like Growth Factor I - metabolism; Lipid Metabolism - drug effects; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oxidation-Reduction; Palmitates - metabolism; Receptors, Somatotropin - antagonists & inhibitors; Vertebrates: endocrinology; Endocrinopathy; Human; Pancreatic hormone; Pegvisomant; Somatotropin hormone; Diseases of the osteoarticular system; Acromegaly; Metabolism; Insulin; Substrate; Sensitivity; Treatment; Adenohypophyseal hormone; Pituitary diseases; Antagonist; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-2276

Context: Pegvisomant is a specific GH receptor antagonist that is able to normalize serum IGF-I concentrations in most patients with acromegaly. The impact of pegvisomant on insulin sensitivity and substrate metabolism is less well described.
Patients and Methods: We assessed basal and insulin-stimulated (euglycemic clamp) substrate metabolism in seven patients with active acromegaly before and after 4-wk pegvisomant treatment (15 mg/d) in an open design.
Results: After pegvisomant, IGF-I decreased, whereas GH increased (IGF-I, 621 ± 82 vs. 247 ± 33 μg/liter, P = 0.02; GH, 5.3 ± 1.5 vs. 10.8 ± 3.3 μg/liter, P = 0.02). Basal serum insulin and plasma glucose levels decreased after treatment (insulin, 54 ± 5.9 vs. 42 ± 5.3 pmol/liter, P = 0.001; glucose, 5.7 ± 0.1 vs. 5.3 ± 0.0 mmol/liter, not significant), whereas palmitate kinetics were unaltered. During the clamp, the glucose infusion rate increased after pegvisomant (3.1 ± 0.5 vs. 4.4 ± 0.6 mg/kg·min, P = 0.02), whereas the suppression of endogenous glucose production tended to increase (0.7 ± 0.0 vs. 0.5 ± 0.1 mg/kg·min, not significant). Total resting energy expenditure decreased after pegvisomant treatment (1703 ± 109 vs. 1563 ± 101 kcal/24 h, P = 0.03), but the rate of lipid oxidation did not change significantly.
Conclusions: 1) Pegvisomant treatment for 4 wk improves peripheral and hepatic insulin sensitivity in acromegaly. 2) This is associated with a decrease in resting energy expenditure, whereas free fatty acid metabolism is unaltered. 3) The data support the important direct effects of GH on glucose metabolism and add additional benefits to pegvisomant treatment for acromegaly.