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
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 =
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
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 =
“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.”