title: Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial.
abstract: OBJECTIVE
  Among patients infected with human immunodeficiency virus (HIV), visceral adiposity is associated with metabolic dysregulation and ectopic fat accumulation. Tesamorelin, a growth hormone-releasing hormone analog, specifically targets visceral fat reduction but its effects on liver fat are unknown.
  
  
  OBJECTIVE
  To investigate the effect of tesamorelin on visceral and liver fat.
  
  
  METHODS
  Double-blind, randomized, placebo-controlled trial conducted among 50 antiretroviral-treated HIV-infected men and women with abdominal fat accumulation at Massachusetts General Hospital in Boston. The first patient was enrolled on January 10, 2011; for the final patient, the 6-month study visit was completed on September 6, 2013.
  
  
  METHODS
  Participants were randomized to receive tesamorelin, 2 mg (n=28), or placebo (n=22), subcutaneously daily for 6 months.
  
  
  METHODS
  Primary end points were changes in visceral adipose tissue and liver fat. Secondary end points included glucose levels and other metabolic end points.
  
  
  RESULTS
  Forty-eight patients received treatment with study drug. Tesamorelin significantly reduced visceral adipose tissue (mean change, -34 cm2 [95% CI, -53 to -15 cm2] with tesamorelin vs 8 cm2 [95% CI, -14 to 30 cm2] with placebo; treatment effect, -42 cm2 [95% CI, -71 to -14 cm2]; P = .005) and liver fat (median change in lipid to water percentage, -2.0% [interquartile range {IQR}, -6.4% to 0.1%] with tesamorelin vs 0.9% [IQR, -0.6% to 3.7%] with placebo; P = .003) over 6 months, for a net treatment effect of -2.9% in lipid to water percentage. Fasting glucose increased in the tesamorelin group at 2 weeks (mean change, 9 mg/dL [95% CI, 5-13 mg/dL] vs 2 mg/dL [95% CI, -3 to 8 mg/dL] in the placebo group; treatment effect, 7 mg/dL [95% CI, 1-14 mg/dL]; P = .03), but changes at 6 months in fasting glucose (mean change, 4 mg/dL [95% CI, -2 to 10 mg/dL] with tesamorelin vs 2 mg/dL [95% CI, -4 to 7 mg/dL] with placebo; treatment effect, 2 mg/dL [95% CI, -6 to 10 mg/dL]; P = .72 overall across time points) and 2-hour glucose (mean change, -1 mg/dL [95% CI, -18 to 15 mg/dL] vs -8 mg/dL [95% CI, -24 to 8 mg/dL], respectively; treatment effect, 7 mg/dL [95% CI, -16 to 29 mg/dL]; P = .53 overall across time points) were not significant.
  
  
  CONCLUSIONS
  In this preliminary study of HIV-infected patients with abdominal fat accumulation, tesamorelin administered for 6 months was associated with reductions in visceral fat and additionally with modest reductions in liver fat. Further studies are needed to determine the clinical importance and long-term consequences of these findings.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01263717.
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Takara L
authors.initials: TL
authors.lastname: Stanley
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Meghan N
authors.initials: MN
authors.lastname: Feldpausch
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Oh
authors.affiliation: Clinical Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Branch
authors.affiliation: Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Martin
authors.initials: M
authors.lastname: Torriani
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Grinspoon
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects; D050154:Adiposity / Q000187:drug effects*; D000328:Adult; D004311:Double-Blind Method; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D013007:Growth Hormone-Releasing Hormone; C479538:tesamorelin