Product description
What is Tesamorelin?
Tesamorelin (also known as TH9507, brand name EGRIFTA) is a synthetic analogue of human growth hormone-releasing hormone (GHRH), consisting of 44 amino acids corresponding to the full sequence of endogenous GHRH with an additional N-terminal modification. The compound was developed by the Canadian company Theratechnologies Inc. and in 2010 received FDA approval as the first and only therapy specifically indicated to reduce excess abdominal fat in adults with HIV-associated lipodystrophy.
Structurally, tesamorelin differs from native GHRH by the presence of a trans-3-hexenoyl group attached to the tyrosine residue at the N-terminus of the molecule. This modification gives the peptide resistance to degradation by the dipeptidyl peptidase 4 (DPP-4) enzyme, which rapidly inactivates native GHRH. As a result, tesamorelin has a significantly longer half-life and better bioavailability after subcutaneous administration. The molecular weight is approximately 5136 Da, and the molecular formula is C₂₂₁H₃₆₆N₇₂O₆₇S.
The mechanism of action of tesamorelin is based on binding to GHRH receptors on pituitary somatotrophs, which stimulates synthesis and pulsatile release of endogenous growth hormone (GH). Unlike direct administration of recombinant GH, pituitary stimulation by tesamorelin preserves the physiological pulsatile secretion pattern and is regulated by the IGF-1 feedback loop.
HIV-associated lipodystrophy, for which tesamorelin is indicated, is characterized by pathological accumulation of visceral adipose tissue (VAT) and loss of subcutaneous fat tissue, occurring in patients receiving highly active antiretroviral therapy (HAART). This metabolic syndrome is associated with increased cardiovascular risk and a significant deterioration in quality of life.
Mechanism of action
GHRH receptor stimulation - Tesamorelin binds to GHRH receptors on pituitary somatotrophs, initiating a signaling cascade involving activation of adenylate cyclase, increased cAMP levels, activation of protein kinase A (PKA), and ultimately GH gene transcription and growth hormone secretion.
Pulsatile GH release - A key advantage of tesamorelin is preservation of the pulsatile GH secretion pattern that mimics physiological release. Each peptide administration induces a rapid rise in plasma GH levels, followed by a return to baseline values.
Selective visceral lipolysis - GH released in response to tesamorelin stimulates lipolysis, especially in visceral adipose tissue. The mechanism involves activation of hormone-sensitive lipase (HSL) and release of fatty acids from adipocytes.
IGF-1 increase - Stimulation of GH secretion leads to increased levels of insulin-like growth factor 1 (IGF-1), which mediates many of GH's anabolic effects.
Effect on hepatic metabolism - Studies have shown that tesamorelin may reduce liver fat content and slow progression of non-alcoholic fatty liver disease (NAFLD) in patients with HIV.
Scientific research directions
Tesamorelin is the subject of intensive clinical research, both in its approved indication and in other potential applications.
HIV-associated lipodystrophy
In two pivotal phase III studies, tesamorelin demonstrated significant efficacy in reducing VAT. After 26 weeks of treatment, the average VAT reduction was approximately 15-18% compared with placebo. The effect depended on continued therapy - patients who discontinued treatment showed reaccumulation of visceral fat.
2025 Meta-analysis
The latest meta-analysis from 2025 confirmed that tesamorelin significantly reduces VAT (mean difference -27.71 cm²), trunk fat (-1.18 kg), and waist circumference (-2.45 cm), while increasing lean body mass (+0.82 kg).
Non-alcoholic fatty liver disease
In a study of patients with HIV and NAFLD, tesamorelin reduced liver fat content and slowed the progression of liver inflammation and fibrosis. A prospective phase II study evaluating tesamorelin in patients with NAFLD regardless of HIV status is ongoing.
New F8 formulation (EGRIFTA WR)
In March 2025, the FDA approved a new tesamorelin formulation (EGRIFTA WR), offering a simplified dosing regimen with weekly reconstitution instead of daily.
Scientific context
Tesamorelin occupies a unique position as the only FDA-approved peptide specifically indicated for the treatment of HIV-associated lipodystrophy. In the context of GH-boosting therapies, the peptide differs from alternative approaches:
- Recombinant GH (somatropin) - directly delivers GH, but causes more adverse effects
- GH secretagogues (GHRP) - act through the ghrelin receptor, stimulate appetite
- Ghrelin mimetics (anamorelin) - approved for cancer cachexia
Tesamorelin offers a “physiological” approach by stimulating endogenous GH secretion while preserving pulsatility and feedback regulation. It is listed on the WADA prohibited substances list.
Safety profile in studies
Overall tolerability - In clinical studies involving more than 900 patients, tesamorelin demonstrated an acceptable safety profile.
Adverse effects - Most commonly observed: hypersensitivity reactions, edema and arthralgia, limb pain, peripheral edema, myalgia, injection-site reactions.
IGF-1 increase - Tesamorelin increases IGF-1 levels, and in some patients values exceeded the upper limit of normal.
Regulatory status - FDA-approved to reduce excess abdominal fat in adults with HIV-associated lipodystrophy. Not approved by the EMA.
Bibliography – latest scientific studies
- Abdallah R et al. Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin in HIV-associated lipodystrophy: A meta-analysis. Obes Med. 2025. ScienceDirect
- FDA. FDA Approves F8 Formulation of Tesamorelin. FDA News. March 2025. FDA
- Stanley TL et al. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients. JAMA. 2014;312(4):380-389. PubMed
- Makimura H et al. Growth hormone and tesamorelin in HIV-associated lipodystrophy. HIV AIDS (Auckl). 2011;3:65-76. PMC
- Falutz J et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-2370. PubMed
- Rochira V, Guaraldi G. Growth hormone deficiency and human immunodeficiency virus. Best Pract Res Clin Endocrinol Metab. 2017;31(1):91-111. PubMed
- Fourman LT et al. Effects of Tesamorelin on Hepatic Transcriptomic Signatures in HIV-Associated NAFLD. JCI Insight. 2020;5(17):e140134. PMC
- Lo J et al. Tesamorelin Decreases Muscle Fat and Increases Muscle Area in Adults with HIV. J Frailty Aging. 2019;8(4):201-206. PubMed
- Spooner LM, Olin JL. Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy. Ann Pharmacother. 2012;46(2):240-247. PubMed
- Dhillon S. Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy. Drugs. 2011;71(8):1071-1091. PubMed
