Tesamorelin

Tesamorelin Peptide

Tesamorelin is a synthetic compound chemically analogous to growth hormone–releasing hormone (GHRH), which has been shown to elevate IGF-1 levels in men by an average of $181 \text{ micrograms per liter}$. It exhibits an affinity for and activation of human GHRH receptors similar to that of the endogenous hormone. Beyond its primary function of stimulating growth hormone release, Tesamorelin shows promise for other potential benefits, including decreasing triglyceride concentrations and enhancing nootropic (cognitive) functions.

Further clinical studies have demonstrated that Tesamorelin can reduce concentrations of C-reactive protein (CRP), decrease carotid intima-media thickness (cIMT), and lower visceral adipose tissue (VAT). Notably, it does not appear to substantially modify the levels or regulatory pathways of other pituitary hormones. Additionally, research suggests Tesamorelin may support cognitive function in elderly individuals and those with mild cognitive impairment—especially in populations at increased risk for the development of Alzheimer’s disease.

Tesamorelin Peptide - Functional Summary

IGF-1 is recognized as the main factor responsible for the anabolic effects of growth hormone, playing a pivotal role in encouraging tissue development and inhibiting programmed cell death. Growth hormone itself facilitates lipolysis—the breakdown of fat—particularly in deposits such as visceral and abdominal fat stores. The mechanism of Tesamorelin is thought to involve binding to GHRH receptors found in the anterior pituitary gland, thereby boosting the secretion of growth hormone and its downstream mediator, IGF-1. Researchers suggest that this binding interaction may result in a change in the receptor’s structure (conformation) and subsequent downstream signaling.

The hypothesis extends to Tesamorelin raising intracellular cyclic AMP (cAMP) levels in target cells by activating the enzyme adenylate cyclase, which converts ATP to cAMP. This increased cAMP level can then activate protein kinase A (PKA), initiating a series of signaling events. This dual activation of the GHRH receptors and the cAMP-PKA cascade is believed to enhance the release and circulation of growth hormone from the somatotroph cells. Published studies have indicated an approximate $69$ increase in overall growth hormone exposure (measured by AUC) and about a $55$ increase in the average pulse area, although the amplitude and frequency of hormone pulses remained unaffected. Moreover, IGF-1 levels were reported to increase by roughly $122$.

Tesamorelin features structural changes on both the C-terminal and N-terminal segments of the GHRH molecule, resulting in improved resistance to enzymatic breakdown and greater stability. The C-terminus is modified with a trans-3-hexenoyl group, a known enzymatic protection feature, and the N-terminus includes an acetyl ($\text{CH}_3\text{CO}$) group, which enhances both its biological activity and stability. Chemically, Tesamorelin is designated as $\text{N-(trans-3-hexenoyl)-[Tyr}^1]\text{hGHRF(1-44)}\text{NH}_2$ acetate.

Clinical Studies of Tesamorelin

Tesamorelin Peptide and Altered Fat Metabolism (Lipodystrophy)

Lipodystrophy is a condition marked by abnormal fat metabolism and uneven fat distribution, leading to fat loss in some areas and excessive fat accumulation in others. It is commonly linked to elevated triglyceride and cholesterol levels and insulin resistance. A Phase III clinical trial monitored 806 participants over 26 weeks, with a 26-week extension phase. Initially, 543 participants were treated with Tesamorelin, and the remainder received a placebo. After the initial 26 weeks, subjects were randomly reassigned for the subsequent treatment phase.

By the completion of the 26-week treatment, Tesamorelin therapy resulted in a significant decrease of at least $15.4$ in visceral adipose tissue. Furthermore, the Tesamorelin group showed notably lower cholesterol and triglyceride levels compared to the placebo group.

Tesamorelin Peptide and Liver Fat in Immunodeficiency

Non-alcoholic fatty liver disease (NAFLD) affects a significant fraction of individuals living with HIV due to their immunodeficient status. In a clinical investigation, 61 HIV-positive subjects with elevated hepatic fat fraction (HFF) were randomly given either Tesamorelin or a placebo over a 12-month period. At the end of the trial, $35$ of the Tesamorelin group achieved a greater than $5$ reduction in HFF, compared to only $4$ of the placebo group showing any decrease. No significant changes were observed in circulating glucose levels.

Tesamorelin Peptide and Cognitive Enhancement

An ongoing clinical investigation is exploring the effect of Tesamorelin on neurological outcomes in immunodeficient subjects with mild cognitive impairment. The trial enrolled 100 participants over 40 years old, who received daily Tesamorelin for six months, followed by a six-month cessation, and then a return to Tesamorelin administration for another six months. The primary metric is the change in the Global Deficit Score after both 6 and 12 months. The final results of this trial are pending publication.

Tesamorelin Peptide and Insulin Resistance in Type 1 Diabetes

A 12-week randomized trial including 53 participants with type 1 diabetes assessed the effect of Tesamorelin on insulin sensitivity. Subjects were allocated to a low-dose, high-dose, or placebo group. After 12 weeks of treatment, no significant differences were observed among the groups in insulin dosage, fasting glucose, or HbA1c levels, suggesting that Tesamorelin did not markedly impact insulin sensitivity under the study conditions.

Tesamorelin Peptide and Musculoskeletal Structure

The effect of Tesamorelin on the structural integrity and composition of muscle was evaluated using Computed tomography (CT) imaging. Measurable and statistically significant changes were observed in targeted muscle groups, including the paraspinal muscles, psoas major, and rectus abdominis. Depending on the muscle group studied, Tesamorelin was associated with either an increase in muscle size and density or a decrease in intramuscular fat content. These observed changes were statistically significant when compared to the placebo group.

Tesamorelin Peptide and Internal Fat Deposits

Visceral obesity is characterized by fat accumulation around and within internal organs, which is frequently observed in individuals with lipodystrophy. This specific pattern of fat deposition is strongly associated with dyslipidemia, impaired glucose metabolism, and insulin resistance. Studies on Tesamorelin have shown reductions in visceral fat of up to $25$ in lipodystrophy models, suggesting a therapeutic role in improving associated metabolic health.