Tesamorelin is a synthetic analogue of human growth hormone-releasing hormone, GHRH(1-44). It is one of the few peptides in this catalogue with a large, published, placebo-controlled human evidence base, because it was developed and approved as a prescription medicine before it became a common research compound. That makes it unusually well characterised, and it also makes it easy to describe inaccurately. This review covers what the molecule is, what the trials measured, and where the limits of that evidence sit.
What Tesamorelin Is
Tesamorelin is the full 44-amino-acid sequence of human GHRH with a single structural modification: a trans-3-hexenoyl group attached to the N-terminal tyrosine. That modification is the entire point of the molecule. Native GHRH(1-44) is cleaved rapidly at the N-terminus by dipeptidyl peptidase IV (DPP-4), leaving it with a circulating half-life measured in minutes. The hexenoyl cap sterically obstructs that cleavage, so the analogue survives long enough in plasma to produce a meaningful signal at the pituitary.
It is, in other words, not a novel agonist. It is native GHRH that has been made to last longer. Everything downstream of the receptor is ordinary GHRH physiology.
What Tesamorelin Does: Mechanism
Tesamorelin binds the GHRH receptor on anterior pituitary somatotrophs. Receptor occupancy raises intracellular cAMP, which drives both synthesis and pulsatile release of endogenous growth hormone. Circulating GH in turn acts on hepatic GH receptors to raise insulin-like growth factor 1 (IGF-1).
The clinically relevant consequence of acting at the GHRH receptor, rather than supplying growth hormone directly, is that the pituitary remains in the loop. GH output stays pulsatile, and negative feedback through somatostatin and IGF-1 is preserved. A GHRH analogue amplifies an existing rhythm; exogenous recombinant GH replaces it with a flat exposure that the feedback loop cannot modulate. This distinction is the main reason GHRH analogues are studied separately from GH itself.
How It Differs From Other Secretagogues
Growth hormone secretagogues split into two mechanistic families, and tesamorelin sits firmly in one of them.
- GHRH analogues (tesamorelin, sermorelin, CJC-1295) act at the GHRH receptor. They differ from one another mainly in how long they survive in plasma.
- GHRPs / ghrelin-receptor agonists (ipamorelin, GHRP-2, GHRP-6) act at GHS-R1a, a different receptor entirely, and additionally suppress somatostatin tone.
Within the GHRH family the practical difference is duration. Sermorelin is GHRH(1-29), the shortest fragment that retains full activity, and is correspondingly short-lived. CJC-1295 with DAC binds covalently to serum albumin and persists for days, which flattens the pulse it was meant to amplify. Tesamorelin occupies the middle: long enough to resist DPP-4, short enough that the pulsatile pattern survives.
What the Published Human Trials Measured
Tesamorelin is the rare research peptide with phase 3 data. It was approved by the FDA in 2010 under the brand name Egrifta, for reduction of excess visceral adipose tissue in HIV-infected patients with lipodystrophy. Two multicentre, randomised, double-blind, placebo-controlled trials underpin that approval.
Falutz and colleagues reported in the New England Journal of Medicine (2007) that 26 weeks of treatment produced a statistically significant reduction in visceral adipose tissue measured by CT, with a corresponding rise in IGF-1 and no significant change in subcutaneous fat. Later analyses reported that the effect was not durable: when treatment stopped, visceral adipose tissue returned toward baseline over the following six months.
Visceral adipose tissue decreased significantly in the tesamorelin group relative to placebo, with IGF-1 levels rising in parallel; discontinuation was followed by reaccumulation.
Two caveats matter when reading that literature. The trials studied a specific clinical population, HIV-associated lipodystrophy, and findings in that group do not transfer automatically to any other. And the endpoints were imaging and serum measurements in a supervised clinical setting, not outcomes observed outside one.
Safety Signals Reported in the Literature
The reported adverse-event profile follows directly from raising GH and IGF-1, and is consistent across the GH-axis literature:
- Glucose regulation: growth hormone is counter-regulatory to insulin. Trials reported changes in glucose tolerance and HbA1c, and glycaemic monitoring was part of the trial protocol.
- Injection-site reactions: the most frequently reported local events, including erythema and pruritus.
- Fluid retention and arthralgia: the familiar consequences of elevated GH, reported across this drug class.
- Contraindications in the label: active malignancy, pituitary disruption, and pregnancy, reflecting the role of the GH/IGF-1 axis in cell proliferation.
Analytical Characterisation
As a 44-residue peptide with an N-terminal acyl modification, tesamorelin is characterised the same way as any peptide of that length: identity by mass spectrometry against the expected monoisotopic mass, and purity by reversed-phase HPLC. The acyl group is the analytically interesting part, since a certificate of analysis that reports only a purity percentage cannot by itself demonstrate that the modification is present and intact. How to read a certificate of analysis covers what each field on that document does and does not establish.
Like other lyophilised peptides it is supplied dry, is hygroscopic, and is handled under the storage conditions described in research peptide storage, shipping and handling.
A Note on Spelling and Naming
The International Nonproprietary Name is tesamorelin. It is frequently written tesamorilin, tesamorelian or tesmorelin, and appears in the literature under the development code TH9507 and the brand name Egrifta. These all refer to the same molecule. The -relin suffix is the standard stem for GHRH analogues, which is why sermorelin and tesamorelin share it.
References & primary sources
The human data cited above come from the phase 3 programme that supported the 2010 FDA approval. Further literature is indexed on PubMed under 'tesamorelin' and 'GHRH analogue'.
- Falutz J, Allas S, Blot K, et al. (2007) Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine 357:2359-2370.
- Falutz J, Mamputu JC, Potvin D, et al. (2010) Effects of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials. Journal of Clinical Endocrinology and Metabolism 95:4291-4304.
- Stanley TL, Feldpausch MN, Oh J, et al. (2014) Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation. JAMA 312:380-389.
- US Food and Drug Administration. Egrifta (tesamorelin for injection) prescribing information. accessdata.fda.gov.
- Ferdinandi ES, Brazeau P, High K, et al. (2007) Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic & Clinical Pharmacology & Toxicology 100:49-58.
Questions and answers
What is tesamorelin?
Tesamorelin is a synthetic analogue of human growth hormone-releasing hormone, GHRH(1-44), carrying a trans-3-hexenoyl group on its N-terminal tyrosine. That modification blocks cleavage by DPP-4, which is what native GHRH is normally degraded by, so the analogue persists in plasma long enough to act at the pituitary.
What does tesamorelin do?
It binds the GHRH receptor on pituitary somatotrophs and stimulates the synthesis and pulsatile release of the body's own growth hormone, which in turn raises IGF-1. Because it acts upstream at the receptor rather than supplying growth hormone directly, pulsatility and normal negative feedback are preserved.
How is tesamorelin different from sermorelin or CJC-1295?
All three are GHRH analogues acting at the same receptor; they differ in how long they last. Sermorelin is the short GHRH(1-29) fragment. CJC-1295 with DAC binds albumin and persists for days, which flattens the GH pulse. Tesamorelin is the full 1-44 sequence stabilised against DPP-4, sitting between the two.
Is tesamorelin FDA approved?
Yes, as a prescription medicine. The FDA approved it in 2010 under the brand name Egrifta for reduction of excess visceral adipose tissue in HIV-infected patients with lipodystrophy. That approval covers that specific clinical indication and population. Material supplied for laboratory research is not a medicine and is not supplied for any therapeutic use.
Why is tesamorelin sometimes spelled tesamorilin?
The correct International Nonproprietary Name is tesamorelin. Variants such as tesamorilin, tesmorelin and tesamorelian are common misspellings of the same molecule, which also appears as TH9507 in the development literature and as Egrifta as a brand name.