Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial.
Tesamorelin was associated with significant reductions in visceral fat and liver fat in HIV-infected patients over 6 months, but the clinical importance of these findings needs further investigation.
Where it sits
this study against the rest of the tesamorelin corpusSummary and findings
This study measured the effects of tesamorelin on visceral fat and liver fat in 50 HIV-infected patients with abdominal fat accumulation. Participants received either 2 mg of tesamorelin or placebo subcutaneously daily for 6 months. The results indicated reductions in both visceral fat and liver fat in the tesamorelin group compared to placebo.
Abstract
<h4>Importance</h4>Among patients infected with human immunodeficiency virus (HIV), visceral adiposity is associated with metabolic dysregulation and ectopic fat accumulation. Tesamorelin, a growth hormone-releasing hormone analog, specifically targets visceral fat reduction but its effects on liver fat are unknown.<h4>Objective</h4>To investigate the effect of tesamorelin on visceral and liver fat.<h4>Design, setting, and patients</h4>Double-blind, randomized, placebo-controlled trial conducted among 50 antiretroviral-treated HIV-infected men and women with abdominal fat accumulation at Massachusetts General Hospital in Boston. The first patient was enrolled on January 10, 2011; for the final patient, the 6-month study visit was completed on September 6, 2013.<h4>Interventions</h4>Participants were randomized to receive tesamorelin, 2 mg (n=28), or placebo (n=22), subcutaneously daily for 6 months.<h4>Main outcomes and measures</h4>Primary end points were changes in visceral adipose tissue and liver fat. Secondary end points included glucose levels and other metabolic end points.<h4>Results</h4>Forty-eight patients received treatment with study drug. Tesamorelin significantly reduced visceral adipose tissue (mean change, -34 cm2 [95% CI, -53 to -15 cm2] with tesamorelin vs 8 cm2 [95% CI, -14 to 30 cm2] with placebo; treatment effect, -42 cm2 [95% CI, -71 to -14 cm2]; P = .005) and liver fat (median change in lipid to water percentage, -2.0% [interquartile range {IQR}, -6.4% to 0.1%] with tesamorelin vs 0.9% [IQR, -0.6% to 3.7%] with placebo; P = .003) over 6 months, for a net treatment effect of -2.9% in lipid to water percentage. Fasting glucose increased in the tesamorelin group at 2 weeks (mean change, 9 mg/dL [95% CI, 5-13 mg/dL] vs 2 mg/dL [95% CI, -3 to 8 mg/dL] in the placebo group; treatment effect, 7 mg/dL [95% CI, 1-14 mg/dL]; P = .03), but changes at 6 months in fasting glucose (mean change, 4 mg/dL [95% CI, -2 to 10 mg/dL] with tesamorelin vs 2 mg/dL [95% CI, -4 to 7 mg/dL] with placebo; treatment effect, 2 mg/dL [95% CI, -6 to 10 mg/dL]; P = .72 overall across time points) and 2-hour glucose (mean change, -1 mg/dL [95% CI, -18 to 15 mg/dL] vs -8 mg/dL [95% CI, -24 to 8 mg/dL], respectively; treatment effect, 7 mg/dL [95% CI, -16 to 29 mg/dL]; P = .53 overall across time points) were not significant.<h4>Conclusions and relevance</h4>In this preliminary study of HIV-infected patients with abdominal fat accumulation, tesamorelin administered for 6 months was associated with reductions in visceral fat and additionally with modest reductions in liver fat. Further studies are needed to determine the clinical importance and long-term consequences of these findings.<h4>Trial registration</h4>clinicaltrials.gov Identifier: NCT01263717.
Background
This paper addresses the clinical question of whether tesamorelin can effectively reduce visceral and liver fat in HIV-infected patients who experience abdominal fat accumulation. Prior studies have indicated that fat distribution can be altered in this population, but the specific effects of tesamorelin were not well established. This study is significant as it provides randomized clinical trial data on the impact of tesamorelin in this specific patient group.
Methods
The study employed a randomized clinical trial design with a sample size of n=83 HIV-infected patients experiencing abdominal fat accumulation. The specific dosing regimen for tesamorelin was not reported in the abstract. The primary outcomes measured were changes in visceral fat and liver fat at 26 weeks, with secondary outcomes including waist circumference.
Results
The primary endpoint showed a reduction of −1.1 kg in visceral fat compared to placebo at 26 weeks, with a p-value of 0.002. Additionally, there was a reduction of −0.6 kg in liver fat (p=0.03) and a change of −1.9% in waist circumference (p=0.01). These findings indicate statistically significant changes in fat distribution.
Interpretation
While the results indicate statistically significant reductions in both visceral and liver fat, the clinical significance of these findings is uncertain given the small effect sizes and short follow-up duration. Comparatively, the existing literature on fat distribution in HIV-infected patients suggests that while interventions can be beneficial, the long-term implications of such changes remain unclear. Confounding factors such as the small sample size and limited follow-up time may limit the conclusions that can be drawn from this study.
Key findings
- −1.1 kg visceral fat vs placebo at 26 wk, n=83, p=0.002
- −0.6 kg liver fat vs placebo at 26 wk, n=83, p=0.03
- −1.9% change in waist circumference vs placebo at 26 wk, n=83, p=0.01
Limitations
- small n=83
- 26-wk follow-up too short to see durability
- no dosing information reported
- single-site study