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.
Level 1 - systematic review of randomized trials
pooled analysis of two multicenter, double-blind, randomized placebo-controlled phase 3 trials
PubMed 20554713 · doi:10.1210/jc.2010-0490
What was done
A pooled analysis of two multicenter, international phase 3 randomized controlled trials evaluated tesamorelin (a growth hormone-releasing factor analog) in 806 antiretroviral therapy (ART)-treated HIV patients with excess abdominal fat. Participants were randomized 2:1 to daily subcutaneous tesamorelin 2 mg (n = 543) or placebo (n = 263) for 26 weeks. At week 26, patients originally receiving tesamorelin were rerandomized to continue tesamorelin (T-T, n = 246) or switch to placebo (T-P, n = 135) for a 26-week extension, while placebo-treated patients switched to tesamorelin (P-T, n = 197). The primary outcome was percent change in visceral adipose tissue (VAT) by CT scan at week 26. Secondary outcomes included abdominal subcutaneous adipose tissue (SAT), lipid parameters, IGF-I, body image ratings, and glucose parameters.
What was found
At week 26, tesamorelin significantly decreased VAT compared with placebo (-24 ± 41 vs. 2 ± 35 cm²; treatment effect: -15.4%, P < 0.001), while SAT did not change significantly (-2 ± 32 vs. 2 ± 29 cm²; treatment effect: -0.6%, P = 0.08). Tesamorelin significantly reduced triglycerides (-37 ± 139 vs. 6 ± 112 mg/dL; treatment effect: -12.3%, P < 0.001) and cholesterol-to-HDL ratio (-0.18 ± 1.00 vs. 0.18 ± 0.94; treatment effect: -7.2%, P < 0.001), while increasing IGF-I (108 ± 112 vs. -7 ± 64 ng/mL, P < 0.001). Body image measures improved (belly appearance distress P = 0.002, patient profile rating P = 0.003, physician profile rating P < 0.001). In the continuous tesamorelin group at week 52, VAT reduction was maintained (-35 ± 50 cm² or -17.5 ± 23.3%), along with decreases in waist circumference (-3.4 ± 6.0 cm), triglycerides (-48 ± 182 mg/dL), cholesterol (-8 ± 38 mg/dL), and non-HDL cholesterol (-7 ± 38 mg/dL; all P < 0.001 vs. baseline). No clinically meaningful differences were observed between groups in glucose parameters at weeks 26 and 52.
Why it matters
Tesamorelin provides a targeted pharmacologic approach that selectively reduces visceral adiposity and improves lipid profiles and body image in HIV patients without exacerbating subcutaneous fat loss.
Limits
The abstract only provides 52-week quantitative outcomes for the continuous treatment arm, omitting detailed data for the crossover and discontinuation arms. Numerical glucose values and specific adverse event rates are not reported in the abstract. Follow-up was restricted to 52 weeks.
Cited by
- supports Tesamorelin stimulates growth hormone release and is uniquely effective at reducing visceral abdominal fat.