Among HIV-infected patients, visceral adiposity is associated with metabolic dysregulation and ectopic fat accumulation. Tesamorelin, a growth hormone-releasing hormone analogue, specifically targets visceral fat reduction, but its effects on liver fat are unknown.
To investigate the effect of tesamorelin on visceral and liver fat.
Design, Setting, and Participants
Fifty antiretroviral-treated HIV-infected men and women with abdominal fat accumulation were recruited for this double-blind, randomized, placebo-controlled trial at Massachusetts General Hospital. The first patient was enrolled on 1/10/2011; the final patient completed his 6 month study visit on 9/6/2013.
Tesamorelin 2mg vs. placebo SC daily for 6 months
Primary endpoints were changes in visceral adipose tissue (VAT) and liver fat. Secondary endpoints included glucose and other metabolic endpoints.
76 patients were screened and 54 randomized. 50 presented for baseline assessment and 48 received treatment with study drug. Tesamorelin significantly reduced VAT (Δ −34 [−53, −15] vs. 8 [−14, 30] cm2, mean [95% CI], tesamorelin vs. placebo, treatment effect −42cm2 [95% CI −71, −14], P = 0.005) and liver fat (Δ −2.0 [−6.4, 0.1] vs. 0.9 [−0.6, 3.7] lipid-to-water %, median [IQR], tesamorelin vs. placebo, P=0.003) over 6 months, for a net treatment effect of −2.9 lipid-to-water %. Fasting glucose increased in the tesamorelin group at 2 weeks (Δ 9 [5, 13] vs. 2 [−3, 8] mg/dL, mean [95% CI], treatment effect 7mg/dL [95% CI 1, 14], P=0.03), but overall changes over 6 months in fasting glucose (Δ 4 [−2, 10] vs. 2 [−4, 7] mg/dL, mean [95% CI], treatment effect 2mg/dL [95% CI −6, 10], P=0.72) and 2 hour glucose (Δ −1 [−18, 15] vs. −8 [−24, 8] mg/dL, mean [95% CI], treatment effect 7mg/dL [95% CI −16, 29], P=0.53) were not significant.
Conclusions and Relevance
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.