Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial
Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK
JAMA (2014) · n=50
First randomized trial to demonstrate that tesamorelin reduces liver fat — not just visceral fat — in HIV-infected adults with abdominal fat accumulation, opening the door to the NAFLD line of investigation that the Grinspoon group has pursued since.
This is the JAMA-published single-center randomized trial that first established tesamorelin as a liver-fat-reducing agent in addition to its known visceral-fat indication. Investigators at Massachusetts General Hospital enrolled 50 antiretroviral-treated HIV-infected adults with abdominal fat accumulation and randomized them to tesamorelin 2 mg subcutaneously daily (n=28) or placebo (n=22) for 6 months. The dual primary endpoints were change in visceral adipose tissue measured by CT and change in liver fat measured by proton magnetic resonance spectroscopy. Tesamorelin produced a 42 cm² greater reduction in visceral adipose tissue than placebo (95% CI -71 to -14 cm²; P=0.005) and a median lipid-to-water percentage change of -2.0% versus +0.9% in placebo (P=0.003). Fasting glucose rose transiently at week 2 (a 7 mg/dL treatment effect) but the difference was not significant at 6 months, and glycemic measures were stable across the trial. The result is conceptually important: it was the first prospective evidence that tesamorelin's GHRH-axis mechanism shrinks ectopic fat depots beyond visceral fat itself, including hepatic fat — a finding that anchored every subsequent NAFLD line of work in the Grinspoon program.
The trial is small (n=50) and single-center, conducted at MGH. The population is still HIV-infected adults with abdominal fat accumulation — generalizability to non-HIV NAFLD is not established by this trial, only by the larger Stanley 2019 follow-up. The 6-month duration is shorter than the regulatory pivotal trials and does not address long-term hepatic outcomes such as fibrosis. The liver-fat measure is imaging-based (proton MRS) rather than histologic; biopsy data is absent. The trial reports a transient early fasting glucose rise that, while not statistically significant at 6 months, is consistent with the known GH-axis insulin-resistance signal and is one of the active monitoring concerns for tesamorelin off-label use. Industry sponsorship was disclosed; Theratechnologies provided the drug. Subsequent fibrosis-progression findings come from Stanley 2019 in Lancet HIV, not from this paper, and readers should not over-read this 6-month liver-fat reduction as evidence of fibrosis benefit on its own. This trial supplies the proof-of-concept that the liver-fat axis matters; the longer-duration Stanley 2019 trial supplies the histology-grade evidence.
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