Tesamorelin Research, Specifications & Scientific Information

Tesamorelin is a synthetic 44-residue analogue of human growth hormone-releasing hormone with a hexenoyl group on its N-terminal tyrosine. It is the one compound in this family with a current United States approval, held by a specific pharmaceutical product in a single HIV-related indication.

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Category: GHRH analogues and GH secretagogues

Introduction

Tesamorelin is the only compound in this part of the catalogue that carries a current regulatory approval, and the approval is worth stating precisely because it is so easily overstated. Tesamorelin for injection is approved in the United States as a pharmaceutical product, marketed as Egrifta, for the reduction of excess abdominal fat in adults with HIV infection and lipodystrophy [6]. That is one indication, one population, one manufactured product and one label. It is not an approval of the molecule in the abstract, and it does not travel to research-grade material.

Structurally it is the outlier of the growth hormone-releasing hormone analogues sold as reagents: where the others are built on the shortened 1-29 fragment, tesamorelin is the whole 44-residue hormone with a single acyl group on its first residue. Its clinical record is correspondingly substantial — two phase 3 trials with more than 800 participants between them, and a continuing programme of investigator-initiated randomised trials in hepatic steatosis. This page sets out what those trials measured.

What Is Tesamorelin?

Tesamorelin is a synthetic 44-residue peptide, developed by Theratechnologies under the code TH9507. The sequence is that of human growth hormone-releasing hormone in full. The modification is at the N-terminus: the tyrosine at position 1 carries a (3E)-3-hexenoyl group, and the C-terminus is an amide.

That single acyl group is the entire design, and its logic is precise. The native hormone is cleaved from its N-terminus at the 2-3 amino acid bond by dipeptidylpeptidase IV, which is why it survives only minutes in plasma [1]. An acyl group on residue 1 obstructs that cleavage without altering the rest of the molecule. Where the CJC-1295 backbone answers the same problem by substituting a D-amino acid at position 2, and CJC-1295 DAC adds albumin binding on top, tesamorelin keeps the native sequence intact and caps the vulnerable end.

The clinical problem it was developed for is specific. Visceral adipose tissue accumulates during antiretroviral therapy in many people with HIV infection, and that accumulation is associated with increased cardiovascular risk [4]. Growth hormone has effects on visceral adipose tissue; a releasing-hormone analogue was pursued as a way of raising endogenous growth hormone rather than administering it.

Tesamorelin Specifications

Compound name
Tesamorelin
Full chemical name
(3E)-Hex-3-enoyl-somatoliberin (human)
Aliases
TH9507, TH-9507, Egrifta, trans-3-hexenoyl-GHRH(1-44) amide, GRF(1-44) analogue
Development code
TH9507
CAS number
218949-48-5
PubChem CID
16137828
UNII
MQG94M5EEO
Compound type
Synthetic modified peptide
Peptide family
Glucagon / secretin peptide superfamily (growth hormone-releasing hormone analogues)
Amino acid sequence
YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL
Sequence length
44 residues
Molecular formula
C221H366N72O67S
Molecular weight
5135.9 g/mol
Primary target
Growth hormone-releasing hormone receptor (GHRHR)
Secondary targets
Not publicly characterised
Receptor family
Class B1 (secretin-like) G protein-coupled receptors
Agonist / antagonist status
Agonist at the GHRH receptor

Tesamorelin is the full 44-residue human growth hormone-releasing hormone sequence, not a shortened fragment, and the chain above is the sequence recorded for it in the FDA/NCATS Global Substance Registration System under UNII MQG94M5EEO. The register carries structural modifications on that chain, the defining one being at position 1, where the tyrosine is acylated with a (3E)-3-hexenoyl group; the C-terminus is an amide. The single-letter string is therefore the backbone rather than the complete covalent structure. That N-terminal acyl group is the whole design: it sits at the end of the molecule attacked by dipeptidylpeptidase IV, the enzyme that clears the native hormone at the 2-3 amino acid bond. CAS registry number 218949-48-5 and PubChem compound identifier 16137828 both resolve to this substance, and the molecular formula and mass agree across those registers and the supplier catalog. The single sulphur atom is the methionine at position 27. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Tesamorelin Work?

The target is the growth hormone-releasing hormone receptor, cloned from human anterior pituitary and characterised as a G protein-coupled receptor signalling through Gs and cyclic AMP [2]. It is a class B1, secretin-like receptor, structurally related to the receptors for glucagon, GLP-1 and secretin, and entirely distinct from the growth hormone secretagogue receptor engaged by ipamorelin and the GHRP hexapeptides.

Activation on a somatotroph produces growth hormone release; circulating growth hormone drives hepatic production of insulin-like growth factor 1. In the registrational trial, IGF-1 rose by 81.0 per cent in the treated group against a fall of 5.0 per cent on placebo, which is the clearest single demonstration that the intended axis was engaged [4].

What distinguishes this compound pharmacologically from administering growth hormone itself is that the pituitary remains in the loop. The axis retains its feedback and its pulsatility, which is the stated rationale for preferring a releasing-hormone analogue in a population where growth hormone administration has its own metabolic liabilities.

Tesamorelin Mechanism of Action

In vitro research

The enzymology that the molecule was designed around was settled two decades before the molecule existed. Plasma degradation of growth hormone-releasing hormone proceeds primarily by dipeptidylpeptidase IV cleavage at the 2-3 amino acid bond; the native 44-residue amide is rapidly cleaved there, a fragment beginning at residue 2 is not, and the conversion is blocked by a competitive inhibitor of the enzyme [1]. Tesamorelin's hexenoyl group is a chemical answer to that specific finding.

The one substantial modern in vitro dataset on this compound is metabolic and analytical. A study of the in vitro metabolism of four larger growth hormone-releasing hormone analogues — sermorelin, tesamorelin and the two CJC-1295 forms — identified nineteen major metabolites across the set, synthesised and characterised them as reference materials, and used them to develop a liquid chromatography-tandem mass spectrometry method with limits of detection generally at or below 1 ng/ml [9].

What Is Tesamorelin Being Researched For?

Published research on tesamorelin covers, in order of how far each has progressed:

  • Excess abdominal fat in HIV-associated lipodystrophy — a phase 2 study across several amounts, two phase 3 trials and a regulatory approval [3, 4, 5, 6].
  • Hepatic steatosis in people with HIV infection — two randomised investigator-initiated trials [7, 8].
  • Interaction with modern antiretroviral regimens — a prespecified analysis among participants on integrase inhibitors [10].
  • Analytical detection — anti-doping method development [9].

All of that is research into a pharmaceutical product, conducted under registered protocols in people with diagnosed HIV infection. None of it is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on Tesamorelin

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Phase 3 trial in HIV-associated abdominal fat accumulation

Population. 412 participants with HIV infection and abdominal fat accumulation, 86 per cent of them men [4, 11].

Endpoint and duration. Randomised to daily subcutaneous administration of 2 mg of tesamorelin or placebo for 26 weeks. Primary endpoint the percentage change from baseline in visceral adipose tissue on computed tomography; secondary endpoints triglycerides, the ratio of total to HDL cholesterol, IGF-1 and self-assessed body image, with glucose and insulin as glycaemic measures [4].

Result. Visceral adipose tissue fell by 15.2 per cent in the treated group and rose by 5.0 per cent on placebo. Triglycerides fell by 50 mg/dL and rose by 9 mg/dL respectively; the total-to-HDL cholesterol ratio fell by 0.31 and rose by 0.21 (p < 0.001 for all three comparisons). IGF-1 rose 81.0 per cent against a 5.0 per cent fall on placebo (p < 0.001). No significant differences were observed in glycaemic measures [4].

Adverse events. Adverse events did not differ significantly between groups, but more participants in the treated group withdrew from the study because of an adverse event [4].

Limitations. Twenty-six weeks, in a population defined by HIV infection and antiretroviral therapy, with an imaging measure as the primary endpoint rather than a clinical outcome.

Second phase 3 trial with a randomised withdrawal extension

Population. 404 participants with HIV infection and excess abdominal fat in the context of antiretroviral therapy, studied between January 2007 and October 2008 [5].

Endpoint and duration. Twelve months in two sequential phases. Months 0 to 6: randomised 2:1 to 2 mg daily subcutaneously or placebo. Months 6 to 12: those on tesamorelin were re-randomised to continue or switch to placebo, and those initially on placebo switched to tesamorelin. Blinding was maintained throughout. Primary endpoint visceral adipose tissue [5].

Result. Over the first six months, visceral adipose tissue fell 10.9 per cent (−21 cm²) against 0.6 per cent (−1 cm²) on placebo (p < 0.0001). Trunk fat, waist circumference and waist-to-hip ratio all improved, with no change in limb or abdominal subcutaneous fat. IGF-1 rose (p < 0.001) with no change in glucose parameters. Participant and physician ratings of abdominal appearance improved (p = 0.02 for both). In those continuing for twelve months, visceral adipose tissue was reduced by approximately 18 per cent (p < 0.001); in those switched to placebo, the six-month improvement was rapidly lost [5].

Adverse events. The authors reported the compound as well tolerated, without significant perturbation of glucose [5].

Limitations. Twelve months in a single disease population. The randomised withdrawal result is the informative part and also the sobering one: the change did not persist after administration stopped.

Randomised trial of visceral and hepatic fat

Population. 50 antiretroviral-treated men and women with HIV infection and abdominal fat accumulation at one centre; 48 received study drug [7, 12].

Endpoint and duration. Double-blind, randomised, placebo-controlled; 2 mg daily subcutaneously (n = 28) or placebo (n = 22) for six months. Co-primary endpoints changes in visceral adipose tissue and liver fat [7].

Result. Visceral adipose tissue changed by a mean of −34 cm² (95% CI −53 to −15) against +8 cm² (95% CI −14 to 30) on placebo, a treatment effect of −42 cm² (95% CI −71 to −14; p = 0.005). Median liver fat, as lipid-to-water percentage, changed by −2.0 per cent (IQR −6.4 to 0.1) against +0.9 per cent (IQR −0.6 to 3.7) on placebo (p = 0.003), a net treatment effect of −2.9 per cent. Fasting glucose rose in the treated group at two weeks (treatment effect 7 mg/dL, 95% CI 1 to 14; p = 0.03) but differences at six months were not significant [7].

Limitations. The authors describe it as a preliminary study of 50 participants at a single centre, and state that further work is needed to determine the clinical importance and long-term consequences of the findings.

Twelve-month trial in HIV-associated non-alcoholic fatty liver disease

Population. 61 people with HIV infection and a hepatic fat fraction of 5 per cent or more by proton magnetic resonance spectroscopy, enrolled between August 2015 and January 2019 at a hospital and a medical research centre in the United States; 30 received tesamorelin and 30 placebo [8, 13].

Endpoint and duration. Randomised 1:1, double-blind, 2 mg once daily or identical placebo for 12 months, followed by a 6-month open-label phase. Primary endpoint change in hepatic fat fraction at 12 months; primary safety endpoint glucose. Analysis by intention to treat [8].

Result. Hepatic fat fraction fell further in the treated group, with an absolute effect size of −4.1 per cent (95% CI −7.6 to −0.7; p = 0.018), a relative reduction from baseline of 37 per cent (95% CI −67 to −7; p = 0.016). At twelve months, 35 per cent of the treated group and 4 per cent of the placebo group had a hepatic fat fraction below 5 per cent (p = 0.0069). Changes in fasting glucose and glycated haemoglobin did not differ between groups [8].

Adverse events. More localised injection-site complaints in the treated group; none were judged serious [8].

Limitations. 61 participants, one disease population, and an authors' conclusion phrased as possibility rather than demonstration, with long-term effects on liver histology explicitly unresolved.

Preclinical Research on Tesamorelin

In vitro research

There is no substantial published animal literature specific to tesamorelin, and this page does not construct one from work on other analogues. The compound moved into clinical study in a defined patient population, and the non-clinical work that bears on it is the enzymology its design answers — dipeptidylpeptidase IV cleavage of growth hormone-releasing hormone at the 2-3 bond, and the demonstration that blocking the N-terminus prevents that cleavage [1].

The other non-clinical dataset is the in vitro metabolism study described above, undertaken to support anti-doping detection rather than to characterise pharmacology [9].

For a compound of this class that is unusual, and it is a consequence of tesamorelin being a medicine: its evidence base is clinical because that is where it was developed.

Other Areas of Tesamorelin Research

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

The registrational programme was conducted before integrase inhibitors became a mainstay of antiretroviral therapy, which left an open question about whether its findings applied to people on current regimens. A prespecified analysis of the 12-month liver trial addressed it: among 38 participants on integrase-inhibitor-based regimens at baseline, 15 on tesamorelin and 16 on placebo completed the study. Visceral fat changed by a median of −25 cm² (IQR −93 to −2) against +14 cm² (IQR 3 to 41) on placebo (p = 0.001); hepatic fat by −4.2 per cent (IQR −12.3 to −2.7) against −0.5 per cent (IQR −3.9 to 2.7) (p = 0.01); and the trunk-to-appendicular fat ratio by −0.1 against 0.0 (p = 0.03). Adverse event frequency, including hyperglycaemia, was similar between groups [10].

The earliest clinical work in the programme was a placebo-controlled study across several administered amounts in the same population, which established the 2 mg daily schedule carried into phase 3 [3].

Two boundaries apply to all of it. Every one of these studies used a pharmaceutical-grade product manufactured to a regulatory standard, administered under a protocol, in people with diagnosed HIV infection and under clinical supervision. And every result concerns that indication: the approval that followed is specific to it and confers nothing elsewhere.

Current Research Status

Regulatory status (United States)
Approved as a pharmaceutical product in one indication. Tesamorelin for injection is approved by the U.S. Food and Drug Administration and marketed as Egrifta for the reduction of excess abdominal fat in adults with HIV infection and lipodystrophy. That approval attaches to a specific manufactured pharmaceutical product, its labelling and that single indication. It does not extend to any other indication, to any other product, or to research-grade material supplied for laboratory use.
Investigational status
Approved and marketed in its labelled indication, and still the subject of investigator-initiated clinical research, chiefly at Massachusetts General Hospital and the National Institutes of Health, in hepatic steatosis in people with HIV infection.
Highest research phase reached
Phase 3 completed; regulatory approval granted in one indication; investigator-initiated randomised trials continuing
Approved uses
Reduction of excess abdominal fat in adults with HIV infection and lipodystrophy, as a specific approved pharmaceutical product.
Approval is compound-specific
Yes

Status as of . This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Chemical & Molecular Characteristics

Tesamorelin is a modified 44-residue peptide, and the register record makes its construction unusually legible.

The chain is the native hormone. YADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARL is the sequence recorded in the FDA/NCATS Global Substance Registration System under UNII MQG94M5EEO and corresponds to human growth hormone-releasing hormone in full. The first 29 residues of it are the sermorelin sequence.

The modification is at residue 1. The register carries a structural modification at position 1, the (3E)-3-hexenoyl group on the N-terminal tyrosine, together with the C-terminal amide. The single-letter string above is therefore the backbone and not the complete covalent structure, and the difference between the two is the compound's entire reason for existing.

The identifiers agree across registers. CAS registry number 218949-48-5 and PubChem compound identifier 16137828 both resolve to this substance, and the molecular formula C221H366N72O67S and molecular weight 5135.9 g/mol are consistent between those registers and the supplier catalog. The single sulphur atom is the methionine at position 27 — the same residue that the CJC-1295 backbone replaces with leucine.

Analytical Specifications

Physical form
Lyophilized powder
Appearance
White to off-white lyophilized solid
Lot number
RP-2609-067
Tested purity
≥99% by HPLC
Storage
−20 °C, protect from light, desiccate

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

What is tesamorelin?
Tesamorelin is a synthetic analogue of human growth hormone-releasing hormone. Unlike the shortened analogues in this family it carries the full 44-residue sequence, with a (3E)-3-hexenoyl group acylating the N-terminal tyrosine. It was developed by Theratechnologies under the code TH9507 and is marketed as a pharmaceutical product under the name Egrifta [6].
Is tesamorelin FDA approved?
Yes, in one indication, and the distinction matters. Tesamorelin for injection is approved by the U.S. Food and Drug Administration for the reduction of excess abdominal fat in adults with HIV infection and lipodystrophy [6, 10]. That approval attaches to a specific manufactured product and its labelling. It does not extend to any other indication, to any other product, or to research-grade material supplied for laboratory use.
How does tesamorelin work?
It is an agonist at the growth hormone-releasing hormone receptor, a class B1 G protein-coupled receptor on pituitary somatotrophs that signals through Gs and cyclic AMP [2]. The hexenoyl group at the N-terminus shields the 2-3 amino acid bond, which is where dipeptidylpeptidase IV cleaves the native hormone within minutes [1]. Raising growth hormone in turn raises insulin-like growth factor 1, which rose by 81 per cent in the registrational trial [4].
What did the registrational trials measure?
Visceral adipose tissue, by computed tomography. In a 26-week randomised placebo-controlled trial of 412 participants with HIV infection and abdominal fat accumulation, the primary endpoint was the percentage change from baseline in visceral adipose tissue; secondary endpoints included triglycerides, the total-to-HDL cholesterol ratio, IGF-1 and self-assessed body image [4, 11].
Has tesamorelin been studied for liver fat?
Yes, in two randomised trials at Massachusetts General Hospital. The first, in 50 participants over six months, measured visceral adipose tissue and liver fat as co-primary endpoints [7]. The second, a 12-month randomised double-blind multicentre trial in 61 people with HIV infection and a hepatic fat fraction of 5 per cent or more, measured change in hepatic fat fraction at 12 months [8, 13].
How does tesamorelin differ from sermorelin?
By length and by the acyl group. Sermorelin is the unmodified first 29 residues of the hormone; tesamorelin is all 44 residues with a hexenoyl group on residue 1. Both act at the same receptor. Tesamorelin holds a current approval; the sermorelin product was withdrawn from the market.
How does tesamorelin differ from CJC-1295?
Different strategies against the same problem. Both address dipeptidylpeptidase IV clearance of the native hormone [1]. Tesamorelin blocks the cleavage site with an N-terminal acyl group on the full-length sequence; CJC-1295 DAC uses amino acid substitutions on a shortened chain plus covalent binding to albumin. Tesamorelin is an approved product; CJC-1295 has never been approved anywhere.
Is tesamorelin still being studied?
Yes. Investigator-initiated randomised work has continued at Massachusetts General Hospital and the National Institutes of Health, most recently examining its effects among participants on integrase-inhibitor antiretroviral regimens, which were not in use when the phase 3 trials were conducted [10].

Scientific References

  1. Frohman LA, Downs TR, Heimer EP, et al.. Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma The Journal of clinical investigation; 1989. PMID 2565342 doi:10.1172/JCI114049
  2. Gaylinn BD, Harrison JK, Zysk JR, et al.. Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone Molecular endocrinology (Baltimore, Md.); 1993. PMID 7680413 doi:10.1210/mend.7.1.7680413
  3. Falutz J, Allas S, Kotler D, et al.. A placebo-controlled, dose-ranging study of a growth hormone releasing factor in HIV-infected patients with abdominal fat accumulation AIDS (London, England); 2005. PMID 16052083 doi:10.1097/01.aids.0000180099.35146.30
  4. Falutz J, Allas S, Blot K, et al.. Metabolic effects of a growth hormone-releasing factor in patients with HIV The New England journal of medicine; 2007. PMID 18057338 doi:10.1056/NEJMoa072375
  5. Falutz J, Potvin D, Mamputu JC, et al.. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension Journal of acquired immune deficiency syndromes (1999); 2010. PMID 20101189 doi:10.1097/QAI.0b013e3181cbdaff
  6. Dhillon S. Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy Drugs; 2011. PMID 21668043
  7. Stanley TL, Feldpausch MN, Oh J, et al.. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial JAMA; 2014. PMID 25038357 doi:10.1001/jama.2014.8334
  8. Stanley TL, Fourman LT, Feldpausch MN, et al.. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial The lancet. HIV; 2019. PMID 31611038 doi:10.1016/S2352-3018(19)30338-8
  9. Memdouh S, Gavrilović I, Ng K, et al.. Advances in the detection of growth hormone releasing hormone synthetic analogs Drug testing and analysis; 2021. PMID 34665524 doi:10.1002/dta.3183
  10. Russo SC, Ockene MW, Arpante AK, et al.. Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors AIDS (London, England); 2024. PMID 38905488 doi:10.1097/QAD.0000000000003965
  11. TH9507 in Patients With HIV-Associated Lipodystrophy 2005. NCT00123253
  12. Effects of Growth Hormone Releasing Hormone in HIV 2010. NCT01263717
  13. Tesamorelin Effects on Liver Fat and Histology in HIV 2015. NCT02196831

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: Tesamorelin specifications and lot documentation