title: Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension.
abstract: BACKGROUND
  HIV-infected patients receiving antiretroviral therapy often demonstrate excess visceral fat. A growth hormone-releasing factor, tesamorelin, may selectively reduce visceral fat in this population. We investigated the effects of tesamorelin (GHRH(1-44)) in HIV-infected patients with central fat accumulation.
  
  
  METHODS
  A 12-month study of 404 HIV-infected patients with excess abdominal fat in the context of antiretroviral therapy was conducted between January 2007 and October 2008. The study consisted of 2 sequential phases. In the primary efficacy phase (months 0-6), patients were randomly assigned to receive tesamorelin [2 mg subcutaneous (SC) every day] or placebo in a 2:1 ratio. In the extension phase (months 6-12), patients receiving tesamorelin were rerandomized to continue on tesamorelin (2 mg SC every day) or switch to placebo. Patients initially randomized to placebo switched to tesamorelin. Patients and investigators were blinded to treatment assignment throughout the study. The primary endpoint was visceral adipose tissue (VAT). Secondary endpoints included body image, IGF-I, safety measures, including glucose, and other body composition measures.
  
  
  RESULTS
  VAT decreased by -10.9% (-21 cm(2)) in the tesamorelin group vs. -0.6% (-1 cm(2)) in the placebo group in the 6-month efficacy phase, P < 0.0001. Trunk fat (P < 0.001), waist circumference (P = 0.02), and waist-hip-ratio (P = 0.001) improved, with no change in limb or abdominal SC fat. Insulin-like growth factor-1 increased (P < 0.001), but no change in glucose parameters was observed. Patient rating of belly appearance distress (P = 0.02) and physician rating of belly profile (P = 0.02) were significantly improved in the tesamorelin vs. placebo-treated groups. The drug was well tolerated. VAT was reduced by approximately 18% (P < 0.001) in patients continuing tesamorelin for 12 months. The initial improvements over 6 months in VAT were rapidly lost in those switching from tesamorelin to placebo.
  
  
  CONCLUSIONS
  Tesamorelin reduces visceral fat by approximately 18% and improves body image distress in HIV-infected patients with central fat accumulation. These changes are achieved without significant side effects or perturbation of glucose.
authors.affiliation: Department of Medicine, Montreal General Hospital and McGill University School of Medicine, Montreal, CA, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Falutz
authors.forename: Diane
authors.initials: D
authors.lastname: Potvin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Mamputu
authors.forename: Hani
authors.initials: H
authors.lastname: Assaad
authors.forename: Monika
authors.initials: M
authors.lastname: Zoltowska
authors.forename: Sophie-Elise
authors.initials: SE
authors.lastname: Michaud
authors.forename: Daniel
authors.initials: D
authors.lastname: Berger
authors.forename: Michael
authors.initials: M
authors.lastname: Somero
authors.forename: Graeme
authors.initials: G
authors.lastname: Moyle
authors.forename: Stephen
authors.initials: S
authors.lastname: Brown
authors.forename: Claudia
authors.initials: C
authors.lastname: Martorell
authors.forename: Ralph
authors.initials: R
authors.lastname: Turner
authors.forename: Steven
authors.initials: S
authors.lastname: Grinspoon
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy*; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D010919:Placebos; D013007:Growth Hormone-Releasing Hormone; C479538:tesamorelin