Two multicenter, double-blind, placebo-controlled clinical trials were conducted in growth hormone-deficient adults. Study 1 was conducted in subjects with adult-onset GHD (n = 166), mean age 48.3 years, at doses of 0.0125 or 0.00625 mg/kg/day; doses of 0.025 mg/kg/day were not tolerated in these subjects. Study 2 was conducted in previously treated subjects with childhood-onset GHD (n = 64), mean age 23.8 years, at randomly assigned doses of 0.025 or 0.0125 mg/kg/day. The studies were designed to assess the effects of replacement therapy with Nutropin on body composition.

Significant changes from baseline to Month 12 of treatment in body composition (i.e., total body % fat mass, trunk % fat mass, and total body % lean mass by DEXA scan) were seen in all Nutropin groups in both studies (p < 0.0001 for change from baseline and vs. placebo), whereas no statistically significant changes were seen in either of the placebo groups. In the adult-onset study, the Nutropin group improved mean total body fat from 35.0% to 31.5%, mean trunk fat from 33.9% to 29.5%, and mean lean body mass from 62.2% to 65.7%, whereas the placebo group had mean changes of 0.2% or less (p = not significant). Due to the possible effect of GH-induced fluid retention on DEXA measurements of lean body mass, DEXA scans were repeated approximately 3 weeks after completion of therapy; mean % lean body mass in the Nutropin group was 65.0%, a change of 2.8% from baseline, compared with a change of 0.4% in the placebo group (p < 0.0001 between groups).

In the childhood-onset study, the high-dose Nutropin group improved mean total body fat from 38.4% to 32.1%, mean trunk fat from 36.7% to 29.0%, and mean lean body mass from 59.1% to 65.5%; the low-dose Nutropin group improved mean total body fat from 37.1% to 31.3%, mean trunk fat from 37.9% to 30.6%, and mean lean body mass from 60.0% to 66.0%; the placebo group had mean changes of 0.6% or less (p = not significant).

In the adult-onset study, significant decreases from baseline to Month 12 in low-density lipoprotein (LDL) cholesterol and LDL:high-density lipoprotein (HDL) ratio were seen in the Nutropin group compared to the placebo group, p < 0.02; there were no statistically significant between-group differences in change from baseline to Month 12 in total cholesterol, HDL cholesterol, or triglycerides. In the childhood-onset study significant decreases from baseline to Month 12 in total cholesterol, LDL cholesterol, and LDL:HDL ratio were seen in the high-dose Nutropin group only, compared to the placebo group, p < 0.05. There were no statistically significant between-group differences in HDL cholesterol or triglycerides from baseline to Month 12.

In the childhood-onset study, 55% of the patients had decreased spine BMD (z-score < –1) at baseline. The administration of Nutropin (n = 16) (0.025 mg/kg/day) for two years resulted in increased spine BMD from baseline when compared to placebo (n = 13) (4.6% vs. 1.0%, respectively, p < 0.03); a transient decrease in spine BMD was seen at six months in the Nutropin-treated patients. Thirty-five percent of subjects treated with this dose had supraphysiological levels of IGF-I at some point during the study, which may carry unknown risks. No significant improvement in total body BMD was found when compared to placebo. A lower GH dose (0.0125 mg/kg/day) did not show significant increments in either of these bone parameters when compared to placebo. No statistically significant effects on BMD were seen in the adult-onset study where patients received GH (0.0125 mg/kg/day) for one year.

Muscle strength, physical endurance, and quality of life measurements were not markedly abnormal at baseline, and no statistically significant effects of Nutropin therapy were observed in the two studies.

A subsequent 32-week, multicenter, open-label, controlled clinical trial was conducted using Nutropin AQ, Nutropin Depot, or no treatment in adults with both adult-onset and childhood-onset GHD. Subjects were randomized into the three groups to evaluate effects on body composition, including change in visceral adipose tissue (VAT) as determined by computed tomography (CT) scan.

For subjects evaluable for change in VAT in the Nutropin AQ (n = 44) and untreated (n = 19) groups, the mean age was 46.2 years and 78% had adult-onset GHD. Subjects in the Nutropin AQ group were treated at doses up to 0.012 mg/kg per day in women (all of whom received estrogen replacement therapy) and men under age 35 years, and up to 0.006 mg/kg per day in men over age 35 years. 

The mean absolute change in VAT from baseline to Week 32 was –10.7 cm2 in the Nutropin AQ group and + 8.4 cm2 in the untreated group (p = 0.013 between groups). There was a 6.7% VAT loss in the Nutropin AQ group (mean percent change from baseline to Week 32) compared with a 7.5% increase in the untreated group (p = 0.012 between groups). The effect of reducing VAT in adult GHD patients with Nutropin AQ on long-term cardiovascular morbidity and mortality has not been determined.