CONTEXT: pegvisomant is a specific GH receptor antagonist, which is able to normalise 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 7 patients with active acromegaly before and after 4 weeks pegvisomant treatment (15 mg/day) in an open design.

RESULTS: After pegvisomant IGF- I decreased, whereas GH increased [IGF-I(µg/l): 621 ± 82 vs. 247 ± 33 µg/l, (P = 0.02); GH (µg/l) 5.3 ± 1.5 vs. 10.8 ± 3.3, (P = 0.02)]. Basal serum insulin and plasma glucose levels decreased after treatment [insulin (pmol/l): 54 ± 5.9 vs. 42 ± 5.3, P = 0.001; glucose (mmol/l) 5.7 ± 0.1 vs. 5.3 ± 0.0, NS], whereas palmitate kinetics were unaltered. During the clamp the glucose infusion rate (mg/kg/min) increased after pegvisomant [3.1 ± 0.5 vs. 4.4 ± 0.6 P = 0.02], whereas the suppression of endogenous glucose production (mg/kg/min) tended to increase [0.7 ± 0.0 vs. 0.5 ± 0.1, NS]. Total resting energy expenditure (kcal/24 h) decreased after pegvisomant treatment [1703 ± 109 vs. 1563 ± 101, P = 0.03], but the rate of lipid oxidation did not change significantly.

CONCLUSION: 1) pegvisomant treatment for 4 weeks improves peripheral and hepatic insulin sensitivity in acromegaly, 2) this is associated with a decrease in resting energy expenditure whereas FFA metabolism is unaltered, 3) the data support the important direct effects of GH on glucose metabolism and add further benefits to pegvisomant treatment for acromegaly