Growth hormone receptor antagonism with pegvisomant in insulin resistant non-diabetic men: A phase II pilot study.

Growth hormone (GH) is known to affect insulin and glucose metabolism.  Blocking its effects in acromegalic patients improves diabetes and glucose metabolism. We aimed to determine the effect of pegvisomant, a GH receptor antagonist, on insulin resistance, endogenous glucose production (EGP) and lipolysis in insulin resistant non-diabetic men.  Four men between the ages of 18-62 with a BMI of 18-35kg/m , with insulin resistance as defined by a HOMA-IR > 2.77, were treated for four weeks with pegvisomant 20 mg daily.  Inpatient metabolic assessments were performed before and after treatment. The main outcome measurements were: change after pegvisomant therapy in insulin sensitivity as measured by hyperinsulinemic euglycemic clamp; and EGP and lipolysis assessed by stable isotope tracer techniques. Insulin like growth factor-1 (IGF-1) concentrations decreased from 134.0 ± 41.5 (mean ± SD) to 72.0 ± 11.7 ng/mL (p = 0.04) after 4 weeks of therapy. Whole body insulin sensitivity index (M/I 3.2 ± 1.3 3.4 ± 2.4; = 0.82), as well as suppression of EGP (89.7 ± 26.9 83.5 ± 21.6%; p = 0.10) and Ra glycerol (59.4 ± 22.1% 61.2 ± 14.4%; p = 0.67) during the clamp were not changed significantly with pegvisomant treatment. Blockade of the GH receptor with pegvisomant for four weeks had no significant effect on insulin/glucose metabolism in a small phase II pilot study of non-diabetic insulin resistant participants without acromegaly.