title: Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin.
abstract: BACKGROUND
  Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue (VAT) by 15%-20% over 6-12 months in individuals with human immunodeficiency virus (HIV)-associated abdominal adiposity, but it is unknown whether VAT reduction is directly associated with endocrine and metabolic changes.
  
  
  METHODS
  In 2 phase III, randomized, double-blind studies, men and women with HIV-associated abdominal fat accumulation were randomly assigned (ratio, 2:1) to receive tesamorelin or placebo for 26 weeks. At week 26, patients initially receiving tesamorelin were randomly assigned to continue receiving tesamorelin or to receive placebo for an additional 26 weeks. In per-protocol analysis of 402 subjects initially randomly assigned to receive tesamorelin, those with ≥8% reduction in VAT were defined a priori as responders per the statistical analysis plan. Post hoc analyses were performed to assess differences between responders and nonresponders.
  
  
  RESULTS
  Compared with tesamorelin nonresponders, responders experienced greater mean (±SD) reduction in triglyceride levels (26 weeks: -0.6 ± 1.7 mmol/L vs -0.1 ± 1.2 mmol/L [P = .005]; 52 weeks: -0.8 ± 1.8 mmol/L vs 0.0 ± 1.1 mmol/L [P = .003]) and attenuated changes in fasting glucose levels (26 weeks: 1 ± 16 mg/dL vs 5 ± 14 mg/dL [P = .01]; 52 weeks: -1 ± 14 mg/dL vs 8 ± 17 mg/dL [P < .001]), hemoglobin A1c levels (26 weeks: 0.1 ± 0.3% vs 0.3 ± 0.4% [P < .001]; 52 weeks: 0.0 ± 0.3% vs 0.2 ± 0.5% [P = .003]), and other parameters of glucose homeostasis. Similar patterns were seen for adiponectin levels, with significant improvement in responders vs nonresponders. Changes in lipid levels and glucose homeostasis were significantly associated with percentage change in VAT.
  
  
  CONCLUSIONS
  In contrast to nonresponders, HIV-infected patients receiving tesamorelin with ≥8% reduction in VAT have significantly improved triglyceride levels, adiponectin levels, and preservation of glucose homeostasis over 52 weeks of treatment. CLINICALTRIALS.GOV REGISTRATION: NCT00123253, NCT00435136, NCT00608023.
authors.affiliation: Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Takara L
authors.initials: TL
authors.lastname: Stanley
authors.forename: Julian
authors.initials: J
authors.lastname: Falutz
authors.forename: Christian
authors.initials: C
authors.lastname: Marsolais
authors.forename: Josée
authors.initials: J
authors.lastname: Morin
authors.forename: Graziella
authors.initials: G
authors.lastname: Soulban
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Mamputu
authors.forename: Hani
authors.initials: H
authors.lastname: Assaad
authors.forename: Ralph
authors.initials: R
authors.lastname: Turner
authors.forename: Steven K
authors.initials: SK
authors.lastname: Grinspoon
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D015658:HIV Infections / Q000188:drug therapy*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control*; D006801:Humans; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D010919:Placebos; D013007:Growth Hormone-Releasing Hormone; C479538:tesamorelin