Metabolic effects of a growth hormone-releasing factor in patients with HIV.

The New England journal of medicine2007PMID: 18057338

Randomized Controlled TrialTesamorelin

Plain Language Summary

Second pivotal 26-week randomized double-blind placebo-controlled trial of tesamorelin 2 mg/day in 412 HIV-positive patients with visceral fat accumulation, demonstrating 15.2% visceral fat reduction by CT, improved triglycerides, improved waist circumference, and patient-reported body image—with no significant worsening of glucose homeostasis. This NEJM publication was one of the two phase III trials supporting FDA approval. Provides the definitive Phase III efficacy and safety evidence for tesamorelin's FDA approval in HIV lipodystrophy—establishing both the magnitude of visceral fat reduction and the absence of clinically meaningful glucose worsening that distinguished tesamorelin from exogenous rhGH and validated the GHRH analog approach.

Abstract

BACKGROUND: Visceral adipose tissue accumulates during antiretroviral therapy in many patients who are infected with the human immunodeficiency virus (HIV); this process is associated with an increased cardiovascular risk. We assessed the use of a growth hormone-releasing factor analogue, tesamorelin, to decrease visceral adiposity. METHODS: We randomly assigned 412 patients with HIV (86% of whom were men) who had an accumulation of abdominal fat to receive a daily subcutaneous injection of either 2 mg of tesamorelin or placebo for 26 weeks. The primary end point was the percent change from baseline in visceral adipose tissue as shown on computed tomography. Secondary end points included triglyceride levels, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, the level of insulin-like growth factor I (IGF-I), and self-assessed body image. Glycemic measures included glucose and insulin levels. RESULTS: The measure of visceral adipose tissue decreased by 15.2% in the tesamorelin group and increased by 5.0% in the placebo group; the levels of triglycerides decreased by 50 mg per deciliter and increased by 9 mg per deciliter, respectively, and the ratio of total cholesterol to HDL cholesterol decreased by 0.31 and increased by 0.21, respectively (P<0.001 for all comparisons). Levels of total cholesterol and HDL cholesterol also improved significantly in the tesamorelin group. Levels of IGF-I increased by 81.0% in the tesamorelin group and decreased by 5.0% in the placebo group (P<0.001). Adverse events did not differ significantly between the two study groups, but more patients in the tesamorelin group withdrew from the study because of an adverse event. No significant differences were observed in glycemic measures. CONCLUSIONS: Daily tesamorelin for 26 weeks decreased visceral fat and improved lipid profiles, effects that might be useful in HIV-infected patients who have treatment-associated central fat accumulation. (ClinicalTrials.gov number, NCT00123253 [ClinicalTrials.gov] .).

Authors

Falutz, Julian; Allas, Soraya; Blot, Koenraad; Potvin, Diane; Kotler, Donald; Somero, Michael; Berger, Daniel; Brown, Stephen; Richmond, Gary; Fessel, Jeffrey; Turner, Ralph; Grinspoon, Steven