Tesamorelin
TH9507
Stabilized GHRH (1-44) analog
About Tesamorelin
Tesamorelin is a synthetic analog of full-length human GHRH (44 amino acids) with a trans-3-hexenoyl group attached to the N-terminal tyrosine, a modification that, in non-clinical studies, made it resistant to inactivation by dipeptidyl peptidase IV (DPP-4).
It stimulates endogenous, pulsatile GH release. It has been approved by the FDA since 2010 for the reduction of excess abdominal fat in patients with HIV and lipodystrophy.
Quick guide · 5 key points
Tesamorelin and visceral fat
Tesamorelin is a stabilized analog of full-length human GHRH, studied mostly for its effect on deep abdominal fat. Here are five things the research shows.
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1
Full-length GHRH, with a chemical shield
Tesamorelin contains the full 44-amino-acid sequence of human GHRH, with a hexenoyl group attached to the first tyrosine. It stimulates the body's own growth hormone (GH) release. It was approved by the FDA in 2010 (Egrifta®) to reduce excess abdominal fat in patients with HIV and lipodystrophy.1
44 aaThe full human GHRH sequence, plus a hexenoyl group -
2
Less visceral fat in a phase 3 trial
In a phase 3 trial of 412 patients with HIV and abdominal fat accumulation, 26 weeks of daily tesamorelin was associated with a 15.2% reduction in visceral fat, compared with a 5.0% increase on placebo. Triglycerides also fell, and IGF-1 rose by 81%.2
−15.2%Visceral fat at 26 weeks, vs +5.0% on placebo -
3
Effect maintained up to 52 weeks
In a pooled analysis of two phase 3 trials (806 patients with HIV), the visceral fat reduction was maintained through week 52 in those who stayed on treatment (−17.5%), with no significant change in subcutaneous fat and improved body image.3
52 wksVisceral fat reduction maintained in the group that continued -
4
Less liver fat, too
In a 12-month randomized trial of 61 people with HIV and non-alcoholic fatty liver disease, tesamorelin was associated with a 37% relative reduction in liver fat vs placebo. 35% reached liver fat below 5%, compared with 4% on placebo.4
−37%Relative reduction in liver fat at 12 months -
5
Known side effects and a short half-life
In the phase 3 trials, the most common side effects were joint pain, injection-site redness and itching, pain in the extremities, peripheral swelling and muscle pain. Injection-site reactions occurred in 24.5% (14.4% on placebo). Glucose intolerance can develop. Its half-life is 26 to 38 minutes.1
24.5%Injection-site reactions, vs 14.4% on placebo
References
- U.S. Food and Drug Administration. Egrifta (tesamorelin for injection) prescribing information. NDA 022505, 2010. Official source
- Falutz J, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-70. PMID 18057338
- Falutz J, et al. 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. J Clin Endocrinol Metab. 2010;95(9):4291-304. PMID 20554713
- Stanley TL, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019;6(12):e821-e830. PMID 31611038
Structure and sequence
Sequence
(trans-3-hexenoyl)-YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL-NH2
Large molecule (5135.9 g/mol): the full structure is shown above; the sequence summarizes its amino-acid order. 3D model available on PubChem.
Five findings from studies
Summary of results reported in the scientific literature. Each finding describes what was observed in the cited study, in its specific population and conditions; it does not constitute a therapeutic indication.
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Clinical study
In a phase 3 trial (412 patients with HIV and abdominal fat accumulation, 26 weeks), a 15.2% reduction in visceral adipose tissue has been shown, versus a 5.0% increase with placebo.
Falutz J et al. N Engl J Med. 2007;357:2359-2370 · PMID 18057338 -
Clinical study
In a pooled analysis of two phase 3 trials, a reduction in visceral fat accompanied by improvements in triglycerides and body image has been observed.
Falutz J et al. J Clin Endocrinol Metab. 2010;95:4291-4304 · PMID 20554713 -
Clinical study
In a randomized trial (50 patients with HIV and abdominal fat accumulation, 6 months), a reduction in visceral fat and a modest reduction in liver fat content versus placebo have been shown.
Stanley TL et al. JAMA. 2014;312:380-389 · PMID 25038357 -
Clinical study
In a 12-month randomized trial in patients with HIV and nonalcoholic hepatic steatosis (61 participants), a 37% relative reduction in hepatic fat fraction versus placebo has been shown, and 35% of treated patients reached liver fat below 5% (versus 4% with placebo).
Stanley TL et al. Lancet HIV. 2019;6:e821-e830 · PMID 31611038 -
Regulatory
Tesamorelin has received FDA regulatory approval (2010) for the reduction of excess abdominal fat in patients with HIV and lipodystrophy.
FDA. Egrifta (tesamorelin) — prescribing information, NDA 022505
