The data were pooled from two trials; a 26-week placebo-controlled primary intervention, and a further 26-week extension safety trial, Dr. Steven Grinspoon at Massachusetts General Hospital, Boston, and colleagues explain in their report in the Journal of Clinical Endocrinology and Metabolism for September, released online June 16.
“This is a novel therapy and the first to our knowledge that specifically reduced excess VAT (visceral adipose tissue) in HIV lipodystrophy,” Dr. Grinspoon told Reuters Health by email
Just over 800 ART-treated HIV patients with excess abdominal fat participated. Initially, two-thirds of the subjects were given tesamorelin and one-third a placebo, which they injected subcutaneously daily (2 mg/d). In the extension trial, the placebo group was given the active agent, while the others were randomized to tesamorelin or placebo.
VAT was assessed by CT scan. At 26 weeks, it had decreased by 24 cm² in the tesamorelin group but increased by 2 cm² in the placebo group. The treatment effect was -15.4% (p<0.001).
Furthermore, triglycerides decreased with tesamorelin (treatment effect -12.3%), as did the total cholesterol to HDL ratio (-7.2%), while the belly profile rated by both patients and physicians improved significantly.
“In fact an important aspect of the study was the improvement in distress related to the excess abdominal fat, an improvement which correlated highly with improvement in the visceral fat,” Dr. Grinspoon noted. “I think subjects were motivated because they are very distressed regarding these changes in fat accumulation and they are eager to improve this condition.”
All the improvements were maintained at 53 weeks in patients who continued on tesamorelin.
Of note, abdominal subcutaneous adipose tissue (SAT) was not affected. “This is important because SAT is increasingly shown to be a beneficial fat depot contributing to improved cardiometabolic risk,” the authors point out.
Why the preferential reduction in VAT rather than SAT? “Treatment resulted in IGF-I levels generally within the normal range,” Dr. Grinspoon explained. “In this setting, the visceral fat may be more sensitive to oxidation in response to increased pulsatile GH, whereas subcutaneous fat may be more resistant. These differences may be due to biological differences in receptor levels, GH/IGF-I action, or metabolic pathways, including lipolytic or oxidative pathways.”
The team cautions that a small percentage of patients using tesamorelin may experience local hypersensitivity reactions, and some may experience glucose increases and signs of GH excess. “Nonetheless,” Dr. Grinspoon and colleagues conclude, “the overall safety profile in over 800 patients was good.”
The treatment is currently under review by the FDA. “In May an advisory panel voted 16-0 in favor of approval, but a final decision on approval is pending by the FDA,” Dr. Grinspoon added. “Once it is approved, it can be used clinically outside of a study, but this has not happened yet.”
J Clin Endocrinol Metab 2010;95)