Reductions in visceral adiposity achieved with tesamorelin therapy are associated with improvements in some key metabolic parameters, according to a study published in the online edition of Clinical Infectious Diseases.
The HIV-positive patients who responded to the therapy had significantly better improvements in their triglyceride levels compared to patients who did not experience meaningful falls in visceral fat levels with tesamorelin. The therapy also had benefits for glucose metabolism.
“The current study suggests that achieving an 8% or greater reduction in visceral adiposity as a result of tesamorelin is associated with metabolic benefits,” write the authors.
Visceral adiposity is a recognised complication of HIV infection and may be a side-effect of some antiretroviral drugs. The impact of the condition on appearance can be distressing. It has also been associated with a worsening of key metabolic parameters and an increased risk of cardiovascular disease.
Therapy with tesamorelin has been shown to reduce visceral adipose fat tissue area by approximately 15% after 26 weeks of therapy, with an 18% reduction seen with 52 weeks of treatment. The drug has also been shown to have some metabolic benefits. These include reductions in levels of triglycerides and non-HDL-cholesterol, as well as increases in adiponectin, a protein produced by fat cells that regulates the metabolism of fats and glucose.
In 2010, the drug was licensed in the US for the treatment of visceral adiposity in HIV-positive patients. Investigators wanted to see if reductions in visceral adipose tissue during tesamorelin therapy were associated with the drug’s metabolic benefits.
The investigators analysed the results of two randomised, placebo-controlled studies that were conducted during the drug’s development.
A decrease of at least 8% in visceral adipose tissue area was defined as a treatment response. The investigators compared metabolic and endocrine parameters in patients according to their response to tesamorelin.
A total of 599 patients were included in study. Outcomes were compared according to response after 26 and 52 weeks.
After 26 weeks, an 8% or greater reduction in visceral adipose tissue was seen in 69% of tesamorelin-treated patients compared to 33% of those in the placebo arm, a significant difference (p < 0.001). By week 52, the proportion of patients treated with tesamorelin who had responded had increased to 72%, but the rate of response had remained unchanged among those receiving the placebo.
Responders experienced significantly greater decreases in waist circumference and trunk fat than non-responders at both week 26 and 52 (p = 0.001 to p < 0.001). Subcutaneous fat levels fell slightly in the responders, but increased slightly in those who did not respond. Non-response was associated with significant gains in limb fat at both week 26 (p < 0.001) and week 52 (p = 0.002).
Levels of insulin-like growth factor-1 (IGF-1) increased significantly more in responders compared to non-responders at week 26 (p < 0.001), but not at week 56. Rates of serious adverse events were 2% in both responders and non-responders. Nevertheless the investigators caution: “As the safety of longer-term tesamorelin use beyond 52 weeks is not known, it is prudent to keep IGF-1 levels within the assay's normal range…to minimize any potential long-term effects associated with tesamorelin use.”
Adiponectin levels were significantly higher in responders than non-responders after 26 weeks (p = 0.011) and 52 weeks (p = 0.008) of therapy.
A bigger reduction in triglyceride levels was observed among the responders at both week 26 and week 52 (p = 0.005; p = 0.003 respectively).
Total cholesterol had fallen in responders but increased in non-responders after 26 weeks (p = 0.014). However, there was no difference between the two groups by week 52.
Levels of fasting glucose were unchanged from baseline in the responders after 26 and 52 weeks. In contrast, levels had increased significantly among the non-responders at both time points, resulting in significant differences in this marker between the two groups (p = 0.01; p < 0.001).
Neither insulin resistance scores nor two-hour glucose levels changed from baseline for the responders. Both increased significantly for non-responders at week 26, and a similar trend was observed after 52 weeks.
HbA1c (a marker of glucose control) levels increased in both responders and non-responders. However, this increase was less severe in responders after 26 weeks (p < 0.001) and 52 weeks (p = 0.003).
“The current report demonstrates that reductions in visceral adipose tissue during tesamorelin therapy are associated with improvements in triglyceride levels, adiponectin levels, and long-term preservation of glucose homeostasis,” conclude the authors. “In contrast, these benefits are not seen in individuals who do not respond to tesamorelin with a reduction in visceral adipose tissue.”
Stanley TL et al. Reduction in visceral adiposity is associated with improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis, online edition. DOI: 10.1093/cid/cis251, 2012.