Metabolic effects of a growth hormone-releasing factor in obese subjects with reduced growth hormone secretion: a randomized controlled trial

Abstract

Context: Obesity is associated with reduced GH secretion and increased cardiovascular disease risk.

Objective: We performed this study to determine the effects of augmenting endogenous GH secretion on body composition and cardiovascular disease risk indices in obese subjects with reduced GH secretion.

Design, patients and methods: A randomized, double-blind, placebo-controlled study was performed involving 60 abdominally obese subjects with reduced GH secretion. Subjects received tesamorelin, a GHRH(1-44) analog, 2 mg once daily, or placebo for 12 months. Abdominal visceral adipose tissue (VAT) was assessed by abdominal computed tomography scan, and carotid intima-media thickness (cIMT) was assessed by ultrasound. Treatment effect was determined by longitudinal linear mixed-effects modeling.

Results: VAT [-16 ± 9 vs.19 ± 9 cm(2), tesamorelin vs. placebo; treatment effect (95% confidence interval): -35 (-58, -12) cm(2); P = 0.003], cIMT (-0.03 ± 0.01 vs. 0.01 ± 0.01 mm; -0.04 (-0.07, -0.01) mm; P = 0.02), log C-reactive protein (-0.17 ± 0.04 vs. -0.03 ± 0.05 mg/liter; -0.15 (-0.30, -0.01) mg/liter, P = 0.04), and triglycerides (-26 ± 16 vs. 12 ± 8 mg/dl; -37 (-67, -7) mg/dl; P = 0.02) improved significantly in the tesamorelin group vs. placebo. No significant effects on abdominal sc adipose tissue (-6 ± 6 vs. 3 ± 11 cm(2); -10 (-32, +13) cm(2); P = 0.40) were seen. IGF-I increased (86 ± 21 vs. -6 ± 8 μg/liter; 92 (+52, +132) μg/liter; P < 0.0001). No changes in fasting, 2-h glucose, or glycated hemoglobin were seen. There were no serious adverse events or differences in adverse events between the groups.

Conclusion: Among obese subjects with relative reductions in GH, tesamorelin selectively reduces VAT without significant effects on sc adipose tissue and improves triglycerides, C-reactive protein, and cIMT, without aggravating glucose.

Trial registration: ClinicalTrials.gov NCT00675506.

Fig. 1.

Enrollment and outcomes. FOBT, Fecal occult blood test.

Fig. 2.

Effects of tesamorelin vs. placebo on IGF-I (A), abdominal VAT area (B), and cIMT (C). Panel A demonstrates the change in IGF-I from baseline over time in tesamorelin vs. placebo. Each point represents mean ± sem of IGF-I in each study group at baseline, 2 wk, and 1, 3, 6, 9, and 12 months. Although IGF-I levels at baseline were similar between the two groups (P = 0.17), IGF-I levels at all subsequent time points were significantly different between each group (P < 0.05 at each time point) with overall P < 0.0001 by longitudinal linear mixed-effects modeling. Panel B demonstrates the difference in VAT between treatment groups with tesamorelin demonstrating a net −19% improvement in VAT compared with placebo. Panel C demonstrates the differences in cIMT between treatment groups with tesamorelin demonstrating a net −6% improvement in cIMT compared with placebo. The T bars in B and C denote the se. Statistical significance was determined by longitudinal linear mixed-effects modeling with the last value carried forward for both B and C.