Tesamorelin

What tesamorelin is

Tesamorelin is a synthetic analogue of human growth hormone-releasing hormone (GHRH, also called growth hormone-releasing factor or GRF). It consists of the full 44-residue sequence of human GHRH(1-44), with the C-terminus amidated as in the native hormone, and a single addition: a trans-3-hexenoyl group attached to the α-amino group of the N-terminal tyrosine [1]. That six-carbon acyl group is the only difference between tesamorelin and the endogenous peptide, and it is the reason the compound exists.

The compound was developed by Theratechnologies of Montréal under the code TH9507 and was licensed by the United States Food and Drug Administration in November 2010 under the brand name Egrifta, for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy [13]. It is, as far as we are aware, the only GHRH analogue to have reached the market as a licensed medicine anywhere. It therefore has a far larger controlled human literature than most compounds in this catalogue, and the distinction between the licensed product and research-grade material has to be drawn clearly, which the regulatory section below does.

Why the hexenoyl group was added is a matter of plain peptide chemistry. Native GHRH has a circulating half-life of only a few minutes, because the enzyme dipeptidyl peptidase-IV (DPP-IV) cleaves the N-terminal dipeptide Tyr1-Ala2 to give GHRH(3-44), which is essentially inactive at the receptor. Acylating the N-terminal amine blocks that cleavage, so the analogue survives longer in plasma while retaining the full native sequence that the receptor recognises. Ferdinandi and colleagues describe the non-clinical pharmacology of TH9507 on this basis: an analogue intended to keep the receptor profile of GHRH with improved resistance to enzymatic degradation, characterised in animal models for its effects on growth hormone and IGF-1 and in a programme of safety studies [1].

Research-grade tesamorelin is supplied as a white lyophilised powder, as the acetate salt. The reference identifiers for the free peptide are in the table; a batch certificate should agree with them within the precision of the method used.

How the literature describes its mechanism

Unlike many compounds in the catalogue, tesamorelin has a defined molecular target. It is an agonist at the GHRH receptor, a class B G-protein-coupled receptor expressed principally on the somatotroph cells of the anterior pituitary. Receptor activation couples through Gs to adenylyl cyclase, raising intracellular cyclic AMP and driving both the synthesis and the release of growth hormone. Because the analogue acts upstream of growth hormone rather than replacing it, the pulsatile pattern of GH secretion and the negative-feedback control exerted by IGF-1 and somatostatin are preserved; this is the pharmacological argument that distinguishes a GHRH analogue from recombinant growth hormone itself. Stanley and Grinspoon's 2015 review of the human studies summarises the position: a GHRH analogue augments basal and pulsatile GH secretion without changing pulse frequency, and the metabolic effects that follow are consistent with a moderate rise in GH and IGF-1 rather than the supraphysiological exposure that exogenous GH produces [12].

The downstream biology is that of growth hormone: lipolysis, most markedly in visceral adipose tissue, and hepatic IGF-1 production. IGF-1 is the marker used in every clinical trial of tesamorelin to confirm target engagement; it rises consistently on treatment, reverses on withdrawal, and the fraction of participants in whom it exceeds the reference range is the most discussed safety variable in the regulatory assessments [5, 6].

The rationale for studying a GHRH analogue in HIV-associated lipodystrophy came from earlier work with the native peptide. Koutkia and colleagues at Massachusetts General Hospital reported in JAMA in 2004 a randomised, placebo-controlled trial of native GHRH(1-29) in 31 HIV-infected men with lipodystrophy over 12 weeks, finding reductions in trunk and visceral fat with an increase in IGF-1 and no significant worsening of glucose [3].

For an in-vitro programme the relevant readouts are receptor-level: cAMP accumulation in cells expressing the human GHRH receptor, competition binding against a labelled GHRH ligand, GH release from primary pituitary cells, and DPP-IV resistance followed directly by LC-MS after incubation with recombinant enzyme or plasma. The native peptide is the natural comparator in each [1].

The research record

Tesamorelin has been through a full regulatory development programme: two phase 3 trials, a pooled analysis, a safety extension, and subsequent investigator-led trials. The record is strong on what the compound does to visceral fat over 6 to 12 months in one population, and much weaker beyond that.

The two phase 3 trials. The first, reported by Falutz and colleagues in the New England Journal of Medicine in 2007, randomised 412 HIV-infected patients with abdominal fat accumulation to tesamorelin or placebo for 26 weeks. Visceral adipose tissue measured by CT fell by about 15% in the tesamorelin group and rose by about 5% in the placebo group; triglycerides fell, IGF-1 rose, and the authors reported no significant difference in glucose parameters between groups over the 26 weeks [4]. The second trial, published in the Journal of Acquired Immune Deficiency Syndromes in 2010, used the same design with a 26-week extension in which responders were re-randomised to continue or switch to placebo. Visceral fat fell by about 11% against roughly 1% on placebo over the primary phase; patients who continued to 52 weeks reached about 18% from baseline, while those switched to placebo regained the fat they had lost [5]. That reversal on withdrawal is reported consistently across the programme.

The pooled analysis. Falutz and colleagues pooled both trials in the Journal of Clinical Endocrinology & Metabolism in 2010, covering 806 patients. The pooled estimate was a visceral fat reduction of around 15% relative to placebo at 26 weeks, maintained in those who continued to 52 weeks, with reductions in triglycerides and total cholesterol and a sustained rise in IGF-1. Glucose and HbA1c showed small differences at some time points that the authors did not regard as clinically significant; adverse events in excess of placebo were mainly injection-site reactions, arthralgia and peripheral oedema, which are the expected class effects of raising GH [6]. The responder analysis by Stanley and colleagues in Clinical Infectious Diseases, using 599 patients from the same trials, found that 69% of tesamorelin-treated patients reached an 8% reduction in visceral fat at 26 weeks against 33% on placebo, and that responders showed better triglyceride, adiponectin and glucose outcomes than non-responders; the authors were careful to present this as an association rather than evidence of causation [7].

IGF-1 and glucose. Two findings run through all of this and deserve to be stated plainly. IGF-1 rises in essentially every treated participant, and in a proportion it rises above the upper limit of the reference range; the European assessors regarded this as a major safety concern given the epidemiological association between high-normal IGF-1 and some cancers, and the absence of long-term data [14]. On glucose, the picture is more reassuring than the GH pharmacology might predict: the phase 3 trials found no clinically meaningful deterioration, and a dedicated 12-week randomised trial by Clemmons and colleagues in 53 patients with type 2 diabetes, published in PLOS ONE in 2017, found no change in the insulin response to oral glucose and no overall worsening of glycaemic control, with a reduction in total and non-HDL cholesterol in the higher-exposure group [11]. These are short studies and do not settle the question of long-term exposure.

Liver fat. The Grinspoon laboratory at Massachusetts General Hospital has pursued the observation that visceral fat reduction might be accompanied by reduction in hepatic fat. Their 2014 JAMA trial in 50 HIV-infected patients with abdominal fat accumulation reported, over 6 months, a reduction in visceral fat together with a reduction in hepatic lipid measured by magnetic resonance spectroscopy [8]. The larger follow-up, published by Stanley and colleagues in The Lancet HIV in 2019, randomised 61 HIV-infected adults with non-alcoholic fatty liver disease to tesamorelin or placebo for 12 months. Hepatic fat fraction fell in the tesamorelin group relative to placebo, and progression of fibrosis on paired biopsy was less frequent in treated participants than in those on placebo [9]. A transcriptomic analysis of the paired liver biopsies from that trial, published in JCI Insight in 2020, reported increased expression of gene sets associated with oxidative phosphorylation and reduced expression of sets associated with inflammation, tissue repair and cell proliferation, correlating with improved fibrosis-related gene scores [10]. These are trials of modest size, the fibrosis finding is a secondary endpoint, and the work is best described as promising and unreplicated.

Cognition. Baker and colleagues reported in Archives of Neurology in 2012 a randomised, placebo-controlled trial of tesamorelin over 20 weeks in 152 older adults, including both healthy participants and participants with mild cognitive impairment. They found a favourable effect on a composite of executive function, with increases in IGF-1 and small changes in glucose and insulin [2]. It is the one substantial study of the compound outside HIV, but it is a single short trial with a composite endpoint and has not been followed by a confirmatory study.

Taking the record as a whole. Tesamorelin has a defined target, a well-characterised mechanism, and controlled trial evidence of a specific, reversible effect on visceral adipose tissue in one patient population over up to a year; consistent evidence of raising IGF-1; short-term evidence of glucose neutrality; and preliminary evidence on liver fat and cognition. What it lacks is long-term safety data, the point on which the European assessment turned [14]. That is a legitimate basis for in-vitro research on GHRH receptor pharmacology. It is not a basis for therapeutic claims about the research material, and this page makes none.

Regulatory status in the United Kingdom

Tesamorelin is not a licensed medicine in the United Kingdom. No product containing it holds a marketing authorisation from the MHRA, and there is no UK monograph for it. The licensed product that exists elsewhere is Egrifta, approved by the US FDA on 10 November 2010 for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy, with approval conditional on further safety studies; it is marketed in the United States and Canada by Theratechnologies [13].

The European position should be stated precisely, because it is often misreported. Egrifta was never refused by the European Medicines Agency; the application was withdrawn. Ferrer Internacional, which held the European rights, submitted a marketing authorisation application to the EMA (EMEA/H/C/002427) and notified the Committee for Medicinal Products for Human Use of its withdrawal on 21 June 2012, after the committee had issued lists of questions and some issues remained unresolved. The EMA's published statement records that the CHMP was provisionally of the view that the product could not have been approved, citing difficulty in distinguishing lipodystrophy-related fat from obesity in practice, insufficient support for the proposed CT-area threshold, doubt about the clinical meaning of the fat reduction, a trial population unrepresentative of European HIV patients, the rise in IGF-1 as a major safety concern, and the absence of long-term safety data [14]. The product has not been resubmitted in Europe, and we are not aware of any application to the MHRA.

BuyUK Peptides supplies tesamorelin as a research chemical for in-vitro laboratory use under the Terms of Sale. Research-grade tesamorelin is not Egrifta: it is not made under a marketing authorisation, is not a sterile pharmaceutical presentation, and carries no claim to the licensed product's clinical properties. It is not for human or veterinary administration. Purchasers must be 18 or over and are responsible for complying with the laws and institutional rules that apply to them. Our guide to the UK rules on research compounds sets this out in more detail.

The World Anti-Doping Agency's Prohibited List, in the 2026 edition effective 1 January 2026, lists under S2.2.4 "growth hormone-releasing factors" the entry "growth hormone-releasing hormone (GHRH) and its analogues (e.g. CJC-1293, CJC-1295, sermorelin and tesamorelin)" [15]. Tesamorelin is therefore named explicitly, and the S2 category is prohibited at all times, in and out of competition. UK Anti-Doping applies the WADA list without modification. Any researcher whose institution is subject to anti-doping rules should be aware of this.

Handling, storage and stability

Tesamorelin is supplied lyophilised in a glass vial with a rubber stopper and an aluminium flip-off crimp. At 44 residues with a methionine, a basic character, and a small hydrophobic acyl group, it is a less forgiving compound than a short unmodified peptide, and the notes below reflect that.

Sealed vial. Store at −20 °C for anything beyond short-term use; 2–8 °C is acceptable for a vial that will be used within weeks. Protect from light. Avoid repeated freeze–thaw cycles. Allow a refrigerated or frozen vial to reach room temperature before opening, so that moisture does not condense onto the cake.

Reconstitution. For most in-vitro work the compound is reconstituted in sterile water or a buffer appropriate to the assay. The free peptide is basic, with an isoelectric point well above neutral, and is readily soluble in water and in mildly acidic buffers; solubility in phosphate-buffered saline at pH 7.2 is reported as sparing, in the range of 1–10 mg/mL [16], so a concentrated stock is better made in water and diluted. Add the solvent down the side of the vial and swirl gently. The reconstitution calculator gives the volume to add for a target concentration.

Reconstituted solution. Keep at 2–8 °C, protect from light, and use within a short period. The particular chemical liabilities of this sequence are oxidation of the methionine at position 27, deamidation of the asparagine and glutamine residues (there are several), and isomerisation at the Asp-Gly motif, all of which proceed faster in solution and at neutral-to-alkaline pH. The hexenoyl group protects the N-terminus against DPP-IV but does nothing for any of these. Aliquoting into single-use volumes and freezing at −20 °C is the sensible approach for a stock that will be used over more than a few days. Discard any solution that becomes cloudy.

Adsorption. A basic 44-residue peptide with a hydrophobic N-terminus adsorbs to glass and some plastics at low concentration. Use low-binding polypropylene for dilute working solutions, a carrier protein where the assay permits, and a low-binding PVDF or PES membrane rather than nylon if filtration is required.

What a sound certificate for tesamorelin looks like

Every batch we release carries an independent certificate of analysis, and the figures from it are transcribed on the product page and in the certificate register. For tesamorelin a certificate should contain the following, and a reader should be able to check each item against this monograph.

Purity by RP-HPLC. Reversed-phase HPLC on a C18 or C8 column with UV detection at 214 or 220 nm reports purity as the area of the main peak as a percentage of all integrated peaks. For a 44-residue peptide a figure of 97% or above is a sound result; 98% and above is achievable. The principal impurities are deletion sequences from synthesis, the methionine sulphoxide (which elutes slightly earlier than the parent on reversed phase), deamidated species, and, specifically for this compound, any un-acylated GHRH(1-44) that escaped the acylation step. A certificate that shows the chromatogram is more informative than one that reports a number alone.

Identity by LC-MS. Electrospray mass spectrometry confirms that the main peak has the expected mass. For tesamorelin the average molecular weight is 5135.9 Da and the monoisotopic mass is 5132.7 Da. A peptide of this size does not appear as a singly charged ion under electrospray; it appears as a series of multiply charged ions, typically from [M+4H]4+ at about 1285.0 through [M+5H]5+ at about 1028.2, [M+6H]6+ at about 857.0 and [M+7H]7+ at about 734.7, and the certificate should report either the charge-state series or a deconvoluted mass. The deconvoluted mass should agree with the theoretical value to within about 1 Da. A species 16 Da heavier indicates methionine oxidation; a species 96 Da lighter than expected indicates the un-acylated native peptide and should prompt a question about the batch.

Net peptide content. Lyophilised peptides contain bound water and counter-ions, usually trifluoroacetate from purification or acetate after an exchange step, so the mass of powder in the vial is more than the mass of peptide. For a basic peptide with many arginine and lysine residues, the counter-ion fraction is significant, and the net peptide content can be in the region of 75–85%. The product page states the nominal peptide mass per vial.

Endotoxin. Where tested, a limulus amoebocyte lysate (LAL) result is reported in endotoxin units per milligram, which matters for cell-based assays of receptor signalling and GH release.

Our guide to reading a certificate of analysis goes through a complete report line by line.

Related compounds

Tesamorelin is one of three GHRH analogues in the catalogue, and the three are best understood together. Sermorelin is GHRH(1-29)-NH2, the shortest fragment that retains full receptor activity, with no stabilising modification; it was itself a licensed diagnostic agent for a period and is the simplest comparator for any receptor assay. CJC-1295 without DAC, also called modified GRF(1-29), takes the opposite approach to the same DPP-IV problem: it substitutes four residues in the 1-29 sequence, including a D-alanine at position 2, rather than acylating the N-terminus. Tesamorelin alone keeps the full native sequence. Ipamorelin is not a GHRH analogue at all but a growth hormone secretagogue acting at the ghrelin receptor (GHS-R1a), which is the other receptor on the somatotroph that drives GH release; the two receptor systems are often studied together because they are synergistic at the pituitary cell.

Frequently asked questions

Is research-grade tesamorelin the same as Egrifta? No. Egrifta is a licensed medicine manufactured under a marketing authorisation to pharmaceutical standards, available in the United States and Canada. Research-grade tesamorelin is the same molecule supplied as a research chemical for in-vitro use, with an independent certificate of analysis but without any pharmaceutical licence or sterile presentation. It is not for human or veterinary administration.

Is tesamorelin licensed in the UK or EU? No. The European application was withdrawn in June 2012 before any opinion was issued, with the CHMP indicating it would not have been approved on the data available [14]. There is no UK marketing authorisation.

What does the hexenoyl group do? It blocks the N-terminal dipeptidyl cleavage by DPP-IV that inactivates native GHRH within minutes in plasma, so the analogue retains the native receptor pharmacology with a longer circulating life [1].

Is it on the WADA list? Yes, named explicitly under S2.2.4 (growth hormone-releasing factors) in the 2026 Prohibited List, prohibited at all times [15].

How long does a sealed vial last? Lyophilised tesamorelin is stable for years at −20 °C and for months at 2–8 °C if kept dry and dark. The batch certificate reports the test date; the storage guidance on this page applies from receipt.

References

1. Ferdinandi ES, Brazeau P, High K, Procter B, Fraser S, Dubreuil P. Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic & Clinical Pharmacology & Toxicology. 2007;100(1):49–58. doi:10.1111/j.1742-7843.2007.00008.x.
2. Baker LD, Barsness SM, Borson S, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Archives of Neurology. 2012;69(11):1420–1429. doi:10.1001/archneurol.2012.1970.
3. Koutkia P, Canavan B, Breu J, Torriani M, Kissko J, Grinspoon S. Growth hormone-releasing hormone in HIV-infected men with lipodystrophy: a randomized controlled trial. JAMA. 2004;292(2):210–218. doi:10.1001/jama.292.2.210. PMID 15249570.
4. Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine. 2007;357(23):2359–2370. doi:10.1056/NEJMoa072375.
5. Falutz J, Allas S, 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. 2010;53(3):311–322. doi:10.1097/QAI.0b013e3181cbdaff. PMID 20101189.
6. Falutz J, Mamputu JC, Potvin D, 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. Journal of Clinical Endocrinology & Metabolism. 2010;95(9):4291–4304. doi:10.1210/jc.2010-0490.
7. Stanley TL, Falutz J, Marsolais C, et al. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clinical Infectious Diseases. 2012;54(11):1642–1651. doi:10.1093/cid/cis251.
8. 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;312(4):380–389. doi:10.1001/jama.2014.8334.
9. 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;6(12):e821–e830. doi:10.1016/S2352-3018(19)30338-8.
10. Fourman LT, Billingsley JM, Agyapong G, et al. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD. JCI Insight. 2020;5(16):e140134. doi:10.1172/jci.insight.140134.
11. Clemmons DR, Miller S, Mamputu JC. Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: a randomized, placebo-controlled trial. PLOS ONE. 2017;12(6):e0179538. doi:10.1371/journal.pone.0179538.
12. Stanley TL, Grinspoon SK. Effects of growth hormone-releasing hormone on visceral fat, metabolic, and cardiovascular indices in human studies. Growth Hormone & IGF Research. 2015;25(2):59–65. doi:10.1016/j.ghir.2014.12.005. PMID 25555516.
13. HIV i-Base. FDA approves tesamorelin for reduction of central fat accumulation. HIV Treatment Bulletin. 1 December 2010. i-base.info/htb/14188.
14. European Medicines Agency. Withdrawal of the marketing authorisation application for Egrifta (tesamorelin). EMEA/H/C/002427. Published 18 July 2012. ema.europa.eu/en/medicines/human/EPAR/egrifta.
15. World Anti-Doping Agency. The 2026 Prohibited List, effective 1 January 2026. Section S2.2.4, growth hormone-releasing factors. wada-ama.org/en/prohibited-list.
16. Cayman Chemical. Tesamorelin (acetate), product information: formula C221H366N72O67S·xC2H4O2, formula weight 5135.9, solubility in PBS pH 7.2 1–10 mg/mL. caymanchem.com/product/42498.

This monograph summarises the published literature for laboratory researchers. It is not medical advice, and nothing on this site is for human or veterinary use.