Analysis of two completed tesamorelin placebo-controlled trials measuring visceral fat density by CT scan—a measure of adipocyte quality—in tesamorelin responders versus placebo-treated HIV patients, finding that tesamorelin improved fat density (reflecting smaller, higher-quality adipocytes) independently of the magnitude of visceral fat volume reduction. Extends tesamorelin's benefits to fat quality beyond fat quantity. Establishes that tesamorelin improves the metabolic quality of visceral adipose tissue beyond simply reducing its volume—suggesting that tesamorelin-treated patients receive additional cardiometabolic benefits from improved adipocyte function even when volume reduction is modest.
Abstract
OBJECTIVES: Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density = smaller, higher quality adipocytes). We assessed the effects of tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PWH), on fat density.
DESIGN: Participants from two completed, placebo-controlled, randomized trials of tesamorelin for central adiposity treatment in PWH were included if they had either a clinical response to tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated.
METHODS: CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader.
RESULTS: Participants (193 responders, 148 placebo) were 87% male and 83% white. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, P = 0.80) and SAT density (-94 HU tesamorelin, -95 HU placebo, P = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in tesamorelin-treated participants only [VAT: +6.2 (8.7) HU tesamorelin, +0.3 (4.2) HU placebo, P < 0.0001; SAT: +4.0 (8.7) HU tesamorelin, +0.3 (4.8) HU placebo, P < 0.0001]. The tesamorelin effects persisted after controlling for baseline VAT or SAT HU and area, and VAT [+2.3 HU, 95% confidence interval (4.5-7.3), P = 0.001) or SAT (+3.5 HU, 95% confidence interval (2.3-4.7), P < 0.001] area change.
CONCLUSION: In PWH with central adiposity who experienced VAT quantity reductions on tesamorelin, VAT and SAT density increased independent of changes in fat quantity, suggesting that tesamorelin also improves VAT and SAT quality in this group.
Authors
Lake, Jordan E; La, Kristen; Erlandson, Kristine M; Adrian, Stefan; Yenokyan, Gayane; Scherzinger, Ann; Dubé, Michael P; Stanley, Takara; Grinspoon, Steven; Falutz, Julian; Mamputu, Jean-Claude; Marsolais, Christian; McComsey, Grace A; Brown, Todd T