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. | Pepdox
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.
Journal of acquired immune deficiency syndromes (1999)2010PMID: 20101189
12-month multicenter randomized placebo-controlled phase III trial of tesamorelin 2 mg/day in 404 HIV-positive patients with excess abdominal fat, demonstrating over 6 months that tesamorelin produced 15.2% VAT reduction versus placebo, with improvements in waist circumference and triglycerides, and that the effect was maintained with continued treatment but reversed upon discontinuation—one of the two pivotal trials supporting FDA approval. First pivotal phase III tesamorelin trial. Establishes tesamorelin's pivotal clinical efficacy in HIV lipodystrophy—demonstrating significant and sustained visceral fat reduction in the largest phase III trial of this drug and characterizing the maintenance requirement (continued treatment) and reversibility of effect upon discontinuation.
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.