Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation.
OBJECTIVE
Treatment of HIV patients with daily tesamorelin, a growth hormone-releasing factor analogue, for 26 weeks resulted in a significant decrease in visceral adipose tissue (VAT) and improvement in lipids. The objective of the 26-week extension phase was to evaluate long-term safety and effects of tesamorelin.


METHODS
HIV patients with central fat accumulation in the context of antiretroviral therapy were randomized to tesamorelin 2 mg (n = 273) or placebo (n = 137) s.c. daily for 26 weeks. At week 26, patients originally on tesamorelin were rerandomized to 2 mg tesamorelin (T-T group, n = 154) or placebo (T-P group, n = 50), whereas patients originally on placebo were switched to tesamorelin (P-T group, n = 111).


METHODS
Safety included adverse events and glucose parameters.


RESULTS
Tesamorelin was generally well tolerated. The prevalence of adverse events and serious adverse events during the extension phase was comparable with the initial phase. Changes in glucose parameters over 52 weeks were not clinically significant and similar to those after 26 weeks. The change in VAT was sustained at -18% over 52 weeks of treatment (P < 0.001 versus baseline) as was the change in triglycerides (-51 mg/dl, P < 0.001 versus baseline). Similar sustained beneficial effects were seen for total cholesterol, but high-density lipoprotein decreased minimally over 52 weeks. Upon discontinuation of tesamorelin, VAT reaccumulated.


CONCLUSIONS
Treatment with tesamorelin was generally well tolerated and resulted in sustained decreases in VAT and triglycerides over 52 weeks without aggravating glucose. Though effects on VAT are sustained during treatment for 52 weeks, these effects do not last beyond the duration of treatment.
Falutz
Julian
J
Montreal General Hospital, McGill University Health Centre, Canada.
Allas
Soraya
S
Mamputu
Jean-Claude
JC
Potvin
Diane
D
Kotler
Donald
D
Somero
Michael
M
Berger
Daniel
D
Brown
Stephen
S
Richmond
Gary
G
Fessel
Jeffrey
J
Turner
Ralph
R
Grinspoon
Steven
S
D052242:Adiponectin / Q000097:blood; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001823:Body Composition; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D050152:Intra-Abdominal Fat / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D044966:Anti-Retroviral Agents; D015415:Biomarkers; D014280:Triglycerides; D002097:C-Reactive Protein; D013007:Growth Hormone-Releasing Hormone; D002784:Cholesterol; C479538:tesamorelin