Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data.
BACKGROUND
HIV patients treated with antiretroviral therapy (ART) often develop increased visceral adipose tissue (VAT).


OBJECTIVE
Our objective was to perform a pooled analysis of two phase-3 studies of tesamorelin in ART-treated HIV patients with excess abdominal fat.


METHODS
Two multicenter, international studies were conducted; a 26-wk randomized, placebo-controlled primary intervention phase was followed by a 26-wk safety extension.


METHODS
A total of 806 ART-treated HIV patients with excess abdominal fat were randomized in a 2:1 fashion to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) sc daily. At wk 26, patients initially on tesamorelin were rerandomized to 2 mg tesamorelin (T-T group, n = 246) or placebo (T-P, n = 135) for an additional 26 wk, whereas patients on placebo were switched to tesamorelin (P-T, n = 197).


METHODS
Tesamorelin (GHRH(1-44)) at a dose of 2 mg or identical placebo, sc, was given daily.


METHODS
We evaluated percent change in VAT by computed tomography scan at wk 26.


RESULTS
At wk 26, VAT decreased significantly in tesamorelin-treated patients (-24 +/- 41 vs. 2 +/- 35 cm(2), tesamorelin vs. placebo, P < 0.001; treatment effect, -15.4%). No significant changes were observed in abdominal sc adipose tissue (-2 +/- 32 vs. 2 +/- 29 cm(2), P = 0.08; treatment effect, -0.6%). Treatment with tesamorelin resulted in significant decreases in triglycerides (-37 +/- 139 vs. 6 +/- 112 mg/dl, P < 0.001; treatment effect, -12.3%) and cholesterol to high-density lipoprotein ratio (-0.18 +/- 1.00 vs. 0.18 +/- 0.94, P < 0.001; treatment effect, -7.2%) vs. placebo. Tesamorelin improved body image [belly appearance distress (P = 0.002)], patient rating of belly profile (P = 0.003), and physician rating of belly profile (P < 0.001). Mean IGF-I increased 108 +/- 112 vs.-7 +/- 64 ng/ml (P < 0.001 vs. placebo). At wk 52, decreases in VAT [-35 +/- 50 cm(2) (-17.5 +/- 23.3%)], waist circumference (-3.4 +/- 6.0 cm), triglycerides (-48 +/- 182 mg/dl), cholesterol (-8 +/- 38 mg/dl), and non-high-density lipoprotein (-7 +/- 38 mg/dl) were maintained (all P < 0.001 vs. original baseline) in the T-T group. Treatment with tesamorelin was generally well tolerated. No clinically meaningful differences were observed between groups in glucose parameters at wk 26 and 52.


CONCLUSIONS
Treatment with tesamorelin reduces VAT and maintains the reduction for up to 52 wk, preserves abdominal sc adipose tissue, improves body image and lipids, and is overall well tolerated without clinically meaningful changes in glucose parameters.
Falutz
Julian
J
Montreal General Hospital, McGill University Health Centre, Montreal H3G 1A4, Canada.
Mamputu
Jean-Claude
JC
Potvin
Diane
D
Moyle
Graeme
G
Soulban
Graziella
G
Loughrey
Helen
H
Marsolais
Christian
C
Turner
Ralph
R
Grinspoon
Steven
S
D050153:Abdominal Fat / Q000187:drug effects / Q000473:pathology; D000328:Adult; D000465:Algorithms; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D004311:Double-Blind Method; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D056128:Obesity, Abdominal / Q000188:drug therapy / Q000209:etiology; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data
D010919:Placebos; D013007:Growth Hormone-Releasing Hormone; C479538:tesamorelin