title: Metabolic effects of a growth hormone-releasing factor in obese subjects with reduced growth hormone secretion: a randomized controlled trial.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.
authors.forename: Hideo
authors.initials: H
authors.lastname: Makimura
authors.forename: Meghan N
authors.initials: MN
authors.lastname: Feldpausch
authors.forename: Alison M
authors.initials: AM
authors.lastname: Rope
authors.forename: Linda C
authors.initials: LC
authors.lastname: Hemphill
authors.forename: Martin
authors.initials: M
authors.lastname: Torriani
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.forename: Steven K
authors.initials: SK
authors.lastname: Grinspoon
mesh_terms: D000293:Adolescent; D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D010919:Placebos; D012307:Risk Factors; D055815:Young Adult
chemical_list: D010919:Placebos; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C479538:tesamorelin