Tesamorelin — identity, handling and published literature

Tesamorelin is a synthetic 44-residue analogue of human growth hormone-releasing hormone, carrying a trans-3-hexenoyl group on the N-terminal tyrosine and a C-terminal amide, supplied as a sterile lyophilised powder for laboratory use.

Presentation and physical properties

The stated vial content refers to peptide mass. Acetate, residual water and any bulking agent contribute additional mass that is not peptide, which is why gravimetric checks on the vial contents do not reconcile against the label figure.

Reconstitution arithmetic

Reconstitution is a dilution calculation and nothing more. The concentration of the resulting solution is the peptide mass in the vial divided by the volume of diluent added:

concentration (mg/mL) = vial content (mg) ÷ diluent volume (mL)

The lyophilised cake occupies negligible volume, so the final volume is taken as the volume of diluent introduced. The table below works this through for a 10 mg vial at three diluent volumes. The right-hand column expresses the same concentration per graduation of a U-100 insulin syringe, on which one unit corresponds to 0.01 mL.

Two arithmetic points follow from the table. Volume and concentration are inversely proportional, so doubling the diluent halves the concentration and halves the peptide mass contained in any fixed volume drawn. And 10 ÷ 3 does not terminate; 3.33 mg/mL is a rounded figure, and rounding it introduces an error of roughly 0.1% relative, which is small against the volumetric error of a hand-drawn syringe graduation.

This section states a mass-per-volume relationship only. It does not indicate what quantity should be withdrawn for any purpose, and no such figure is given anywhere in this entry.

Storage and stability

Lyophilised. The dry solid is the stable form. Peptides of this class are held frozen for long-term storage and at refrigerated temperature for shorter periods, protected from light and from moisture. The powder is hygroscopic; allowing a cold vial to reach ambient temperature before the closure is broken limits condensation onto the cake, which is the usual route by which water reaches a lyophilisate that was meant to stay dry.

In solution. Once reconstituted the molecule is markedly less stable and is held refrigerated. Degradation in solution proceeds by chemical routes rather than by any single dramatic event, so a solution that has degraded generally looks unchanged.

Degradation routes specific to this sequence. The residue composition determines what fails first:

• Methionine oxidation. The sequence contains a single methionine, at position 27. Thioether oxidation to the sulfoxide is the most probable oxidative modification, adds 16 Da, and is promoted by dissolved oxygen, trace transition metals and light.
• Asparagine and glutamine deamidation. There are two asparagine residues (positions 8 and 35) and five glutamine residues (positions 16, 24, 30, 31 and 36). Deamidation converts the amide side chain to a carboxylate, adds approximately 1 Da, introduces a negative charge and is accelerated at neutral to alkaline pH. Asn-Gly and Asn-Ser motifs deamidate fastest; this sequence contains Asn8-Ser9, so that site is a plausible first point of loss.
• Aspartate isomerisation and aspartimide formation. Aspartate at positions 3 and 25 can cyclise to a succinimide intermediate and open to the iso-aspartyl form. This is mass-neutral, so it is invisible to a total-mass measurement and shows only as a chromatographic shoulder.
• C-terminal amide hydrolysis. Loss of the Leu44 carboxamide adds approximately 1 Da and changes the terminal charge.
• N-terminal acyl group. The trans-3-hexenoyl moiety is the defining structural feature of this analogue relative to native GHRH. Its loss regenerates an unmodified N-terminus and yields a different molecule, so integrity of that modification is an identity question rather than only a purity question.
• Aggregation and surface adsorption. At low concentration, peptides adsorb appreciably onto glass and plastic surfaces, which depletes dilute solutions without any chemical change occurring.

Freeze–thaw. Repeated freeze–thaw cycling of solutions is a recognised source of loss for peptides generally, through concentration of solutes and pH excursion at the freezing front, and through interfacial denaturation. The absence of any disulfide bond removes disulfide scrambling from the list of possible failures, but does nothing to protect against the routes above.

Analytical identity

RP-HPLC. Reversed-phase chromatography on a C18 stationary phase with a water/acetonitrile gradient and an acidic ion-pairing modifier is the standard separation. It resolves the intact peptide from deletion sequences, oxidised forms and the isoaspartyl variant, the last of which frequently appears as a partially resolved shoulder rather than a separate peak.

Ultraviolet detection. The sequence contains no tryptophan. Absorbance at 280 nm therefore depends on two tyrosine residues alone and is weak, which makes 280 nm a poor basis for quantification of this particular peptide. Detection at 214–220 nm, which responds to the amide backbone, is the practical choice.

Mass spectrometry. The average molecular mass is 5135.9 for the free base, formula C₂₂₁H₃₆₆N₇₂O₆₇S. Electrospray ionisation of a molecule with six arginine and two lysine residues produces a multiply charged envelope rather than a single ion. Calculated from the average mass, the principal expected m/z values are:

These are average-mass figures. A high-resolution instrument reports the monoisotopic series instead, which for a molecule of this size sits several mass units below the average value because of the ¹³C contribution, and the two must not be compared directly. Confirmation of sequence, as distinct from confirmation of mass, requires tandem MS fragmentation; intact mass alone cannot distinguish this peptide from an isomer, and specifically cannot detect aspartate isomerisation, which is mass-neutral.

Analytical methods for GHRH analogues in biological matrices, including immunoaffinity enrichment and nano-scale liquid chromatography coupled to high-resolution mass spectrometry, have been reviewed in the anti-doping literature [16].

What area-percent purity does and does not measure. A purity figure quoted as area-percent by HPLC is the integrated area of the main peak divided by the total integrated area, at one detection wavelength. It is a statement about the relative proportion of chromophore-bearing species that eluted and were detected. It is not a statement about peptide content, which is the fraction of the vial mass that is peptide at all — acetate, water and bulking agents are chromatographically invisible and can account for a substantial share of the gross mass. Area-percent also cannot see species that do not elute under the method, co-elute with the main peak, or lack absorbance at the detection wavelength; it says nothing about endotoxin, residual solvents, elemental impurities or microbiological quality; and it cannot confirm that the main peak is the intended sequence. Peptide content by amino acid analysis or quantitative NMR, and identity by mass spectrometry, answer different questions and are not substitutes for one another.

What the published literature investigated

In vitro and non-clinical models

A 2007 non-clinical evaluation described the molecule under its development code TH9507 and reported that the trans-3-hexenoyl modification at Tyr1 conferred resistance to dipeptidyl aminopeptidase-IV. The same report described slowed in vitro degradation in rat, dog and human plasma, and prolonged plasma elimination kinetics of the immunoreactive peptide in vivo. Increases in plasma growth hormone and insulin-like growth factor-1 were reported in pigs, rats and dogs following repeat administration, and subchronic toxicity studies of up to four months in rats and dogs reported an increase in body weight gain that the authors described as significant but not dose-related [1]. A 2004 study examined pulmonary delivery of the same compound in the dog [2].

Human trials — visceral adipose tissue in HIV-associated lipodystrophy

The clinical literature is dominated by a single programme. A 2005 placebo-controlled dose-ranging study in people with HIV and abdominal fat accumulation reported dose-related increases in IGF-1 and reductions in truncal fat [3].

A 2007 multicentre randomised placebo-controlled trial enrolled 412 participants with HIV and abdominal fat accumulation over 26 weeks, with percentage change in visceral adipose tissue on computed tomography as the primary endpoint. The trial reported a 15.2% decrease in visceral adipose tissue in the treated group against a 5.0% increase under placebo, alongside changes in triglycerides and in the ratio of total to HDL cholesterol, and an 81.0% increase in IGF-1 [4].

A 2010 pooled analysis combined two multicentre double-blind placebo-controlled phase 3 trials, together comprising 806 participants receiving antiretroviral therapy, with a 26-week randomised phase followed by a 26-week safety extension [5]. A 2026 meta-analysis of randomised controlled trials examined body composition, hepatic fat, metabolic and safety outcomes across this literature [6].

Human trials — hepatic fat

A 2014 randomised double-blind placebo-controlled trial in 50 antiretroviral-treated adults with HIV and abdominal adiposity, run over six months, reported a reduction in visceral fat and what the authors characterised as modest reductions in liver fat, with a transient elevation in fasting glucose at two weeks that had resolved by the end of the study [7].

A 2019 randomised double-blind multicentre trial enrolled 61 participants with HIV and non-alcoholic fatty liver disease over 12 months. It reported a greater reduction in hepatic fat fraction than placebo, an absolute difference of −4.1%, and that 35% of the treated group reached a normal hepatic fat fraction against 4% of controls. Injection-site reactions were reported more frequently in the treated group [9].

Two mechanistic analyses drew on that trial population: a 2020 study of hepatic transcriptomic signatures [10], and a 2021 study reporting effects on circulating markers of immune activation alongside hepatic immune pathways [11].

Human trials — other endpoints and populations

A 2019 analysis reported effects on muscle fat and muscle area in adults with HIV [12]. A 2024 study examined outcomes in people with HIV receiving integrase inhibitors [13].

A 2025 randomised study in 73 virally suppressed participants with HIV and abdominal obesity examined neurocognitive impairment over six months. It reported a reduction in waist circumference but no significant difference between groups in cognitive outcomes [14].

A 2026 double-blind placebo-controlled pilot trial in 22 participants, with baseline cognition ranging from normal to mild cognitive impairment, assessed cognition and brain connectivity over 10 weeks [15].

Outside HIV, a 12-week randomised placebo-controlled study published in 2017 enrolled 53 participants with type 2 diabetes and examined safety and metabolic endpoints including insulin sensitivity, glucose control and lipid measures [8].

Evidence gaps and limitations

The gaps in this literature are specific, documented and in one case stated by a regulator.

The human evidence base is almost entirely one clinical population. With the exception of a single 12-week study in type 2 diabetes [8] and a 22-participant cognition pilot [15], every substantial randomised trial listed above was conducted in people living with HIV who had abdominal fat accumulation on antiretroviral therapy. Nothing in that body of work establishes what happens in any other population, and it should not be read as though it does.

A regulator has explicitly declined to conclude on the benefit–risk balance. The European marketing authorisation application, submitted on 31 May 2011, was withdrawn on 26 June 2012 while under review by the Committee for Medicinal Products for Human Use. The stated reason was that the CHMP considered the data submitted did not allow it to conclude on a positive benefit–risk balance. Two specific deficiencies were identified: an absence of safety data beyond 48 weeks bearing on sustained elevation of IGF-1, and the absence of any cardiovascular endpoint against which to evaluate the risk–benefit ratio. Those two gaps have not since been filled by any trial in the record above.

Long-term consequences of sustained IGF-1 elevation are unresolved. The 2007 trial reported an 81.0% increase in IGF-1 [4]. No trial in this literature was designed or powered to detect low-frequency long-term outcomes associated with prolonged elevation of that axis, and the longest randomised exposures on record are of the order of 12 months.

Reported cognitive findings are null or preliminary. The largest randomised examination of neurocognitive endpoints reported no significant between-group difference [14]. The 2026 pilot is 22 participants over 10 weeks and is described by its authors as a pilot [15]. Neither supports a general conclusion.

There is no published head-to-head comparison against other GHRH analogues or growth hormone secretagogues, so the literature offers no basis for ranking this compound against related molecules.

Non-clinical data are old and narrow. The principal non-clinical characterisation dates from 2007 [1], and the subchronic toxicity work described there extends to four months in two species. No modern comprehensive toxicological package is in the public literature.

All of the above concerns pharmaceutical-grade material. Every trial cited used product manufactured under pharmaceutical quality systems, with defined identity, content, impurity profile, endotoxin limits and sterility. Findings from those trials are statements about that material. They cannot be assumed to transfer to research-grade powder of any provenance, whose impurity profile, peptide content and microbiological quality are different questions requiring separate evidence.

Regulatory and standards position

United Kingdom. Tesamorelin holds no marketing authorisation from the Medicines and Healthcare products Regulatory Agency. There is no UK-authorised medicinal product containing this substance, and therefore no UK medicine to which it corresponds. It is not a controlled drug under the Misuse of Drugs Act 1971 and is not scheduled under the Misuse of Drugs Regulations 2001. The absence of a marketing authorisation does not place the substance outside medicines law: under the Human Medicines Regulations 2012, and consistently with MHRA Guidance Note 8, a product may be a medicinal product by presentation on the basis of the claims made for it, independently of its composition. A claim, not the molecule, is what engages that regime.

European Union. A centralised marketing authorisation application for tesamorelin was submitted on 31 May 2011 and withdrawn by the applicant on 26 June 2012, before any authorisation was granted. The application was under CHMP review at the time of withdrawal. There is accordingly no EU authorisation, and there never has been.

United States. Tesamorelin was approved by the Food and Drug Administration in November 2010 under the brand name Egrifta, for a named indication relating to excess visceral adipose tissue in HIV-associated lipodystrophy. Reformulated presentations have subsequently been approved. A United States approval confers no authorisation status in the United Kingdom.

Anti-doping. Tesamorelin is named explicitly in the World Anti-Doping Agency Prohibited List at S2.2.4, Growth hormone releasing factors, within the bullet covering growth hormone-releasing hormone and its analogues, alongside CJC-1293, CJC-1295 and sermorelin. Section S2 substances are prohibited at all times, both in competition and out of competition. Analytical methods for detecting GHRH analogues in urine and blood are an established and active area of anti-doping method development [16].

Laboratory handling and safety

This material is a laboratory chemical of incompletely characterised toxicology and should be handled on that basis.

• Personal protective equipment. Safety spectacles, nitrile gloves and a laboratory coat as a minimum. Handle the dry lyophilisate in a manner that avoids generating airborne powder; where dispersal is possible, work in a containment device or fume hood with appropriate respiratory protection.
• Reconstitution. Introduce diluent slowly against the vial wall rather than directly onto the cake, and dissolve by gentle swirling or inversion. Vigorous agitation and vortexing drive interfacial denaturation and foaming, both of which cause peptide loss. Do not shake.
• Spills. Dry powder should be contained rather than swept, which re-aerosolises it: dampen, collect with absorbent material, and decontaminate the surface. Liquid spills should be absorbed and the area cleaned. Retain all contaminated absorbent for disposal as chemical waste.
• Disposal. Dispose of unused material, contaminated consumables and sharps as chemical and clinical waste under local regulations and the institution’s waste procedures. Do not dispose of peptide solutions to drain.
• Record-keeping. Maintain records of receipt, supplier and reference or batch identifier, storage location and temperature, date and volume of reconstitution, calculated concentration, subsequent storage conditions, freeze–thaw cycles, and final disposal. Label every reconstituted vial with the compound, the calculated concentration and the date of reconstitution — reconstituted vials are otherwise indistinguishable from one another, and the concentration is the one property that cannot be recovered by inspection.
• Segregation. Store separately from foodstuffs and from any material intended for human or veterinary use, and label the storage location so that the research-use status is unambiguous to anyone else with access.

References

1. Ferdinandi ES, Brazeau P, High K, Procter B, Fennell 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. Model: in vitro plasma stability, rat, dog and pig. PMID 17214611
2. Jansen M, Darby I, Abribat T, Dubreuil P, Ferdinandi ES, Hardy JG. Pulmonary delivery of TH9507, a growth hormone releasing factor analogue, in the dog. International Journal of Pharmaceutics. 2004;276(1–2):75–81. Model: dog. PMID 15113616
3. Falutz J, Allas S, Kotler D, Thompson M, Koutkia P, Albu J, Trottier B, Routy JP, Cote P, Abribat T, Grinspoon S. A placebo-controlled, dose-ranging study of a growth hormone releasing factor in HIV-infected patients with abdominal fat accumulation. AIDS. 2005;19(12):1279–87. Model: human randomised controlled trial. PMID 16052083
4. Falutz J, Allas S, Blot K, Potvin D, Kotler D, Somero M, Berger D, Brown S, Richmond G, Fessel J, Turner R, Grinspoon S. Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine. 2007;357(23):2359–70. Model: human multicentre randomised controlled trial, n=412. PMID 18057338
5. Falutz J, Mamputu JC, Potvin D, Moyle G, Soulban G, Loughrey H, Marsolais C, Turner R, Grinspoon S. 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. Model: human, pooled analysis of two phase 3 trials, n=806. PMID 20554713
6. Badran AS, Helal A, Shata KS, Ayesh H. Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: A meta-analysis of randomized controlled trials. Obesity Research & Clinical Practice. 2026;20(1):2–12. Model: meta-analysis of human randomised controlled trials. PMID 41545261
7. Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK. 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. Model: human randomised controlled trial, n=50. PMID 25038357
8. 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. Model: human randomised controlled trial, n=53. PMID 28617838
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. Lancet HIV. 2019;6(12):e821–e830. Model: human randomised controlled trial, n=61. PMID 31611038
10. Fourman LT, Billingsley JM, Agyapong G, Ho Sui SJ, Feldpausch MN, Purdy J, Zheng I, Pan CS, Corey KE, Torriani M, Kleiner DE, Hadigan CM, Stanley TL, Chung RT, Grinspoon SK. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD. JCI Insight. 2020;5(16). Model: human, transcriptomic analysis within a randomised trial. PMID 32701508
11. Stanley TL, Fourman LT, Wong LP, Sadreyev R, Billingsley JM, Feldpausch MN, Zheng I, Pan CS, Boutin A, Lee H, Corey KE, Torriani M, Kleiner DE, Chung RT, Hadigan CM, Grinspoon SK. Growth hormone releasing hormone reduces circulating markers of immune activation in parallel with effects on hepatic immune pathways in individuals with HIV-infection and nonalcoholic fatty liver disease. Clinical Infectious Diseases. 2021;73(4):621–630. Model: human, analysis within a randomised trial. PMID 33852720
12. Adrian S, Scherzinger A, Sanyal A, Lake JE, Falutz J, Dubé MP, Stanley T, Grinspoon S, Mamputu JC, Marsolais C, Brown TT, Erlandson KM. The growth hormone releasing hormone analogue, tesamorelin, decreases muscle fat and increases muscle area in adults with HIV. Journal of Frailty & Aging. 2019;8(3):154–159. Model: human. PMID 31237318
13. Russo SC, Ockene MW, Arpante AK, Johnson JE, Lee H, Toribio M, Stanley TL, Hadigan CM, Grinspoon SK, Erlandson KM, Fourman LT. Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors. AIDS. 2024;38(12):1758–1764. Model: human. PMID 38905488
14. Ellis RJ, Vaida F, Hu K, Dube M, Henry B, Chow F, Heaton RK, Lee D, Sattler F. Effects of tesamorelin on neurocognitive impairment in persons with HIV and abdominal obesity. Journal of Infectious Diseases. 2025;231(5):1230–1238. Model: human randomised study, n=73. PMID 39813152
15. Stewart CE, French KP, Wright TJ, Wilhoit K, Randolph KM, Danesi CP, Gilkison CR, Karmonik C, Lu L, Dillon EL, Durham WJ, Urban RJ, Sheffield-Moore M, Masel BE. The effect of growth hormone-releasing hormone on cognition and brain connectivity in adults with cognition ranging from normal to mild cognitive impairment. eNeurologicalSci. 2026;44:100616. Model: human double-blind placebo-controlled pilot trial, n=22. PMID 42382101
16. Memdouh S, Gavrilović I, Ng K, Cowan D, Abbate V. Advances in the detection of growth hormone releasing hormone synthetic analogs. Drug Testing and Analysis. 2021;13(11–12):1871–1887. Model: analytical methods review. PMID 34665524

Research use only

This entry is a record of published literature and physicochemical data, compiled for reference. It is not guidance and it is not advice.

Tesamorelin is supplied strictly as a laboratory chemical for research use only. It is not authorised as a medicine in the United Kingdom, it is not for human or veterinary administration, and it is not for use in food, in cosmetics, or in any household application. Nothing in this entry is a claim that the substance treats, prevents, cures or improves any condition, and no such claim is made or implied. Where a study is described, the description is a statement about what that study reported, not a statement about what the substance does.

Handling should be undertaken only by persons with appropriate training, in an appropriate facility, in accordance with local regulations and institutional procedures.