Plain Language Summary
12-month randomized double-blind placebo-controlled trial of tesamorelin 2 mg/day in 60 non-HIV abdominally obese adults with reduced GH secretion, demonstrating that tesamorelin significantly reduced visceral fat and improved carotid intima-media thickness—a cardiovascular disease surrogate—compared to placebo, establishing tesamorelin's efficacy and cardiovascular risk reduction potential in non-HIV obesity with GH deficiency. Established tesamorelin's efficacy in non-HIV obesity with GH deficiency. Demonstrates that tesamorelin's visceral fat reduction and cardiovascular risk benefits extend to non-HIV patients with obesity-related GH deficiency—suggesting broader therapeutic applications beyond HIV lipodystrophy and providing the basis for evaluating tesamorelin in metabolic syndrome and type 2 diabetes.
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.
Authors
Makimura, Hideo; Feldpausch, Meghan N; Rope, Alison M; Hemphill, Linda C; Torriani, Martin; Lee, Hang; Grinspoon, Steven K