Tesamorelin

C221H366N72O67S

N-((3E)-hex-3-enoyl)-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

Key Benefits

Targets
Visceral Fat

Particularly effective in reducing visceral adipose tissue without significantly affecting subcutaneous fat. This targeted action is critical for treating conditions like lipodystrophy, where excess visceral fat is a major health concern.

Natural Pulse GH Release

Stimulates the natural pulsatile release of GH. This mimicking of the body's natural GH secretion pattern is crucial for maintaining the effectiveness of GH therapy over time and reduces the risk of adverse effects associated with non-pulsatile GH release, such as receptor desensitization or altered metabolic outcomes.

Minimal Impact on Glucose

Has been shown to have minimal effects on fasting glucose and insulin levels. This aspect is particularly advantageous in treating patients who may already be at risk for diabetes or other metabolic disorders, ensuring that the treatment for excess visceral fat does not adversely impact glycemic control.

Insulin-Like Growth Factor 1 (IGF-1)

The increase in IGF-1 levels following Tesamorelin administration helps to improve protein synthesis and muscle growth, which is particularly beneficial in clinical scenarios where muscle wasting or metabolic dysfunction is a concern.

Biologic Description

Tesamorelin is a sophisticated analog of human growth-hormone-releasing hormone (GHRH), specifically designed to enhance the secretion of growth hormone (GH) with remarkable specificity and pharmacological efficacy. It stands out in its class by virtue of its structural modifications and receptor-targeting precision.

Tesamorelin is a 44-amino acid peptide that includes a strategic trans-3-hexenoyl modification at its N-terminus, which significantly improves its affinity for the GHRH receptor on somatotroph cells in the anterior pituitary gland. This receptor, a G-protein-coupled receptor (GPCR), specifically binds GHRH and its analogs, activating intracellular signaling cascades that are crucial for GH synthesis and release.

Binding of Tesamorelin to the GHRH receptor triggers the exchange of GDP for GTP on the Gs protein associated with the receptor, leading to the activation of adenylate cyclase. The resultant increase in cyclic AMP (cAMP) levels activates protein kinase A (PKA), which phosphorylates the cAMP response element-binding protein (CREB). Phosphorylated CREB binds to cAMP response elements in the promoter regions of specific genes, including the GH1 gene responsible for encoding growth hormone. This transcriptional activation is central to the production of growth hormone within the pituitary gland.

The pulsatile release of GH induced by Tesamorelin stimulates systemic physiological effects, primarily mediated through GH receptors in various tissues, including liver, muscle, and adipose tissue. GH interacts with these receptors to promote lipolysis and inhibit lipogenesis, specifically targeting visceral fat cells. Additionally, GH stimulates the liver to produce insulin-like growth factor 1 (IGF-1), a key mediator of growth hormone's effects on cell growth and metabolism.

Tesamorelin exhibits a half-life of approximately 20-30 minutes, which is conducive to mimicking the natural pulsatility of GHRH, making it an effective treatment for reducing visceral adipose tissue without significantly impacting subcutaneous fat. This property is particularly valuable in the management of HIV-associated lipodystrophy, where excessive visceral fat accumulation poses health risks.

Unlike other GHRH analogs, Tesamorelin’s efficacy and safety are enhanced by its high receptor specificity, which minimizes the potential for off-target effects commonly associated with broader systemic hormonal alterations. Its unique ability to stimulate GH secretion while maintaining the natural pulsatile release pattern differentiates it from continuous GH or GHRH agonists, which can lead to

It represents a targeted approach to modulating the GH axis, offering significant therapeutic benefits through a carefully engineered peptide structure, precise receptor engagement, and effective induction of key signaling pathways and genetic mechanisms. Its clinical utility in reducing visceral fat while sparing peripheral fat makes it a unique tool in the management of specific metabolic disorders.

Dosage Guidelines

For the administration of Tesamorelin in a research setting, particularly in studies involving GH dynamics or the treatment of conditions like lipodystrophy, begin with an introductory dose of 1 mg to assess tolerance.

This dose should be administered subcutaneously, late at night, ideally at least 90 minutes after eating to minimize interactions with food-induced hormonal variations.

If well tolerated, the dose can be escalated to 2 mg per session, based on the subject's response and the specific objectives of the research. This standard therapeutic dose aims to ensure an effective reduction of visceral fat while monitoring GH and IGF-1 levels.

Administer Tesamorelin five nights per week, preferably before bedtime to mimic the natural peak of nocturnal GH release, enhancing the physiological relevance of the exogenous GH peak. The injection should be given subcutaneously in the abdominal area, rotating sites to prevent lipoatrophy or irritation.

The administration should follow a cyclical pattern, with cycles typically lasting 3-6 months depending on the specific research objectives. Regular monitoring of GH and IGF-1 levels, glucose metabolism, and lipid profiles is crucial to adjust dosing and cycle length appropriately. Baseline and periodic assessment of liver function tests and lipid panels are also recommended to ensure safety and efficacy.

Tesamorelin should not be administered indefinitely. Periods of discontinuation are advised to assess the long-term effects of therapy on the GH axis recovery and to mitigate potential adverse effects.

1-2 mg

Five Days On
2 Days Off

3 Months

Side Effects

Tesamorelin is associated with a range of side effects, most of which relate to its mechanism of action as a growth hormone-releasing hormone analog. The most commonly reported side effects include injection site reactions such as redness, itching, swelling, and irritation. These are typically mild and resolve without intervention, but rotating the injection site can help minimize discomfort.

In addition to localized reactions, Tesamorelin can cause systemic effects due to its influence on growth hormone levels. Patients may experience headaches, muscle pain, and joint discomfort, which are symptoms often associated with changes in growth hormone levels. Some individuals may also report feelings of fatigue or insomnia, likely related to the body's adaptation to altered hormone levels.

Gastrointestinal issues such as nausea, vomiting, and diarrhea have also been reported, although these are less common. These symptoms might be linked to the body's response to increased growth hormone levels, which can affect gastrointestinal function.

It is important to avoid use in individuals with known hypersensitivity to tesamorelin or any of its excipients, and caution is advised in patients with pituitary dysfunction, malignancy, or those at risk for acromegaly.

Due to its stimulatory effect on growth hormone production, Tesamorelin may cause increased blood sugar levels, making glucose monitoring important, particularly in patients with diabetes or those at risk for diabetes. Long-term use of Tesamorelin could potentially lead to an increase in insulin resistance.

Hypersensitivity reactions, though rare, can occur and include symptoms like rash, hives, difficulty breathing, and severe dizziness. These reactions require immediate medical attention as they can be life-threatening.

Furthermore, because Tesamorelin stimulates growth hormone production, there is a theoretical risk of promoting tumor growth, particularly in individuals with undiagnosed or residual malignancies. Patients with active or a history of cancer should be closely monitored or may be advised against the use of Tesamorelin.

Overall, while Tesamorelin is effective for reducing visceral fat and improving metabolic parameters in patients with lipodystrophy, it is crucial for patients and healthcare providers to be aware of its potential side effects. Monitoring and management of these side effects are key to maximizing the therapeutic benefits of Tesamorelin while minimizing risks to the patient.

References:

Falutz, J., Allas, S., Blot, K., Potvin, D., Kotler, D., Somero, M., Berger, D., Brown, T., Richmond, G., Fichtenbaum, C., Turner, R., Grinspoon, S. (2010). Metabolic effects of tesamorelin in patients with HIV-associated lipodystrophy: a randomized, placebo-controlled trial. The Journal of Clinical Endocrinology & Metabolism, 95(9), 4291-4304. https://doi.org/10.1210/jc.2010-0490
Stanley, T. L., Falutz, J., Marsolais, C., Morin, J., Soulban, G., Mamputu, J. C., & Grinspoon, S. (2017). Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. Journal of the American Medical Association, 318(7), 626-635. https://doi.org/10.1001/jama.2017.12268
Koutkia, P., Meininger, G., Canavan, B., Breu, J., & Grinspoon, S. (2004). Metabolic regulation by growth hormone: A pilot study in patients with HIV lipodystrophy. Journal of Clinical Endocrinology & Metabolism, 89(4), 2189-2196. https://doi.org/10.1210/jc.2003-031457
Mangili, A., Falutz, J., Mamputu, J. C., Potvin, D., & Moyle, G. (2016). Effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine, 355(23), 2359-2370. https://doi.org/10.1056/NEJMoa067215