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Tesamorelin

Tesamorelin: A Stabilised GHRH(1–44) Analogue Approved for HIV-Associated Lipodystrophy

Research summary. Tesamorelin is a stabilised synthetic analogue of full-length human growth hormone-releasing hormone (GHRH, residues 1–44), modified at the N-terminus with a trans-3-hexenoyl group to confer resistance to dipeptidyl peptidase-4 cleavage. It is the only GHRH analogue currently FDA-approved as a marketed drug, having been approved in 2010 (Egrifta, Theratechnologies) for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy. Tesamorelin acts on pituitary somatotrophs through the same physiological GHRH-receptor pathway as endogenous GHRH, producing pulsatile GH and IGF-1 increases without the architecture-disrupting effects of direct exogenous GH administration.

Molecular profile

  • Sequence: Trans-3-hexenoyl-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH₂ (full GHRH(1–44) sequence with N-terminal trans-3-hexenoyl modification)
  • Molecular formula: C₂₂₃H₃₇₀N₇₂O₆₉S
  • Molecular weight: ~5195.9 g/mol
  • PubChem CID: 44147413
  • CAS number: 901758-09-6
  • Class: Stabilised GHRH(1–44) analogue; GHRH receptor agonist
  • Synonyms: Egrifta (brand name); TH9507; Theratropin
  • Approval: FDA-approved 2010 (Egrifta) for HIV-associated lipodystrophy

Mechanism of action

Tesamorelin engages the GHRH receptor through the physiological GHRH pathway:

  • GHRH receptor agonism. Binds the GHRH receptor (a class B GPCR) on pituitary somatotrophs, triggering Gαs-mediated cAMP elevation. This drives both immediate vesicular GH release and longer-term GH gene transcription.
  • DPP-4 resistance via N-terminal modification. Endogenous GHRH(1–44) is rapidly cleaved by dipeptidyl peptidase-4. The trans-3-hexenoyl modification at Tyr1 blocks DPP-4 cleavage, extending plasma half-life and supporting once-daily subcutaneous dosing.
  • Pulsatile GH release. Like Sermorelin (GHRH(1–29)), tesamorelin acts via the physiological pathway and supports pulsatile GH release subject to IGF-1 and somatostatin negative feedback — a fundamental difference from exogenous recombinant GH administration.
  • Selective effect on visceral adiposity. The clinical observation of preferential reduction in visceral adipose tissue (VAT) — the basis for the FDA approval — reflects GH/IGF-1-axis effects on lipolysis and on lipid handling in deep abdominal fat depots.

Clinical and preclinical research highlights

HIV-associated lipodystrophy. The pivotal Phase 3 trials (Falutz et al., NEJM 2007) reported that tesamorelin substantially reduced visceral adipose tissue (approximately 15–20% reduction over 26 weeks) in HIV-infected adults with lipodystrophy, supporting FDA approval in 2010.

Continued clinical use. Tesamorelin has remained the standard FDA-approved pharmacological intervention for HIV-associated visceral adiposity, with long-term extension studies supporting durability of effect with continued administration.

Mild cognitive impairment. Tesamorelin has been studied in research investigating GH-axis effects on cognition in mild cognitive impairment and early Alzheimer's-type pathology, with reported improvements in some cognitive endpoints. This research is investigational and is not the basis for any approved indication.

MASH / NAFLD. Tesamorelin has been studied in MASH and non-alcoholic fatty liver disease, with reported reductions in hepatic fat content and improvements in some liver-injury markers. These findings are investigational.

Adverse effect profile. Reported adverse effects include injection-site reactions, arthralgia, peripheral oedema, and small increases in fasting glucose. As with other GH-axis modulators, attention to glucose tolerance is appropriate during sustained use.

Current research status

Tesamorelin is FDA-approved for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy (Egrifta, 2010). Research-grade tesamorelin is supplied for laboratory use only and is distinct from the regulated drug product.

For research-supplier contexts, tesamorelin research material is supplied as a research-grade peptide and is not a substitute for the regulated drug product.

Key takeaways for researchers

  • Tesamorelin is a stabilised GHRH(1–44) analogue with an N-terminal trans-3-hexenoyl modification conferring DPP-4 resistance.
  • It is FDA-approved as Egrifta (2010) for the reduction of excess abdominal fat in HIV-associated lipodystrophy — the only GHRH analogue currently approved as a marketed drug.
  • The mechanism is GHRH-receptor-mediated pulsatile GH release, distinct from exogenous recombinant GH administration.
  • Research interest extends to mild cognitive impairment and MASH, but tesamorelin is not approved for these indications.
  • Research-grade tesamorelin is for laboratory use only and is not a substitute for the regulated drug product.

References

  1. 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. N Engl J Med. 2007;357(23):2359–2370.
  2. Stanley TL, Falutz J, Mamputu JC, Soulban G, Potvin D, Grinspoon SK. Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: relationship with visceral adipose reduction. AIDS. 2011;25(10):1281–1288.

This article is provided for educational and research purposes only. Tesamorelin research material is supplied for laboratory use and is not intended for human consumption outside of the approved, regulated drug product (Egrifta). It is not intended for diagnosis, treatment, cure, or prevention of any disease or condition. All work involving this peptide should be conducted by qualified personnel within an appropriate research setting and in compliance with applicable institutional and regulatory requirements.

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