www.hivandhepatitis.com

Visceral Fat Reduction in HIV+ People on Tesamorelin Improves Metabolic Profile

The synthetic growth hormone-releasing factor tesamorelin (Egrifta) reduces internal abdominal fat in people with HIV, which in turn leads to improvements in lipid and glucose levels, researchers reported in the June 2012 issue of Clinical Infectious Diseases.

Many people with HIV have unusual accumulation of deep abdominal fat surrounding the internal organs, though its cause it not well understood. Human growth hormone (GH) reduces visceral fat, but is associated with serious side effects. Tesamorelin (formerly TH9507) stimulates the pituitary gland to secrete GH, maintaining more stable and natural levels than direct administration of GH itself. Clinical trials have shown that it significantly reduces visceral abdominal fat by 15%-20% over 6-12 months with fewer side effects than GH, though fat typically returns after the drug is discontinued.

Takara Stanley and Steven Grinspoon from Massachusetts General Hospital and colleagues explored whether tesamorelin-induced visceral fat reduction is directly associated with endocrine and metabolic changes.

The researchers performed a post hoc (after the fact) analysis of data from 2 Phase 3 randomized clinical trials of tesamorelin vs placebo in men and women with HIV-associated abdominal fat accumulation. After 26 weeks, patients initially receiving tesamorelin were randomly assigned to either continue receiving tesamorelin or switch to placebo for an additional 26 weeks.

The overall analysis included approximately 600 people. In a per-protocol analysis of about 400 patients initially assigned to receive tesamorelin, those with at least an 8% reduction in visceral adipose tissue (VAT) were defined as responders. The present analysis assessed differences in several metabolic and endocrine laboratory parameters between responders and non-responders.

Results

·      At 26 weeks, 69% of tesamorelin recipients achieved at least an 8% reduction in VAT, compared with 33% of those taking placebo.

·      At 52 weeks, the corresponding proportions of responders were 72% and 33%, respectively.

·      Tesamorelin responders had a significantly greater mean reduction in triglycerides compared with non-responders: -0.6 vs -0.1 mmol/L, respectively, at 26 weeks (P = 0.005); -0.8 vs 0.0 mmol/L at 52 weeks (P = 0.003).

·      Total cholesterol decreased among responders and increased among non-responders at 26 weeks -- a significant difference (P = 0.014) -- but levels were statistically similar at 52 weeks.

·      Responders had minimal changes in fasting glucose, while non-responders saw increases: 1 vs 5 mg/dL at 26 weeks (P = 0.01); -1 vs 8 mg/dL at 52 weeks (P < 0.001).

·      Insulin-like growth factor-1 (IGF-1) levels were significantly higher among responders compared with non-responders at 26 weeks, but not at 52 weeks.

·      Hemoglobin A1c levels increased less among responders than among non-responders: 0.1 vs 0.3 at 26 weeks (P < 0.001]; 0.0 vs 0.2 at 52 weeks (P = 0.003).

·      Insulin resistance scores remained stable among responders but increased significantly among non-responders at 26 weeks, with a similar trend at 52 weeks.

·      Levels of adiponectin (a hormone produced by fat tissue) were significantly higher -- indicating improvement -- in responders compared with non-responders at 26 weeks (P = 0.011) and 52 weeks (p = 0.08).

·      Changes in lipid and glucose levels were significantly associated with percentage change in VAT.

·      Rates of adverse events were similar and low (2%) in the responder and non-responder groups.

Based on these findings, the investigators concluded, "In contrast to non-responders, 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."

6/22/12

Reference

TL Stanley, J Falutz, C Marsolais, SK Grinspoon, et al. Reductionin visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clinical Infectious Diseases 54(11):1642-1651. June 2012.