Description

Tesamorelin Peptide

For Research & Laboratory Use Only

Overview

Tesamorelin is a synthetic 44–amino acid peptide designed as an analog of endogenous growth hormone–releasing hormone (GHRH). Its sequence incorporates specific N- and C-terminal modifications that are thought to enhance stability and resistance to enzymatic degradation compared to native GHRH.(1,4)

Functionally, Tesamorelin has been studied for its potential to:

• Bind to GHRH receptors on somatotroph cells in the anterior pituitary

• Increase endogenous growth hormone (GH) secretion

• Elevate circulating insulin-like growth factor-1 (IGF-1) levels(1,3)

Once released, GH acts on multiple target tissues, including the liver and peripheral organs, where it may stimulate both systemic and local IGF-1 production. IGF-1 is considered a primary anabolic mediator of GH, while GH itself is regarded as lipolytic, especially in visceral and abdominal adipose depots.(1)

Mechanism of Action – GH/IGF-1 Axis and cAMP Signaling

Tesamorelin appears to mimic the action of GHRH at its receptor, triggering GHRH receptor–mediated signaling in the anterior pituitary.(1,3)

Proposed steps include:

1. Receptor Binding & Conformational Change
   Tesamorelin binds to the GHRH receptor, likely inducing a conformational shift that initiates intracellular signaling.

2. Activation of Adenylate Cyclase
   Receptor activation is thought to stimulate adenylate cyclase, converting ATP into cyclic adenosine monophosphate (cAMP).

3. cAMP → PKA Activation
   Increased cAMP may activate protein kinase A (PKA), a key kinase involved in downstream signal propagation.

4. Hormone Release from Somatotrophs
   PKA-mediated phosphorylation of target proteins is believed to enhance GH secretion from pituitary somatotroph cells and promote its distribution in circulation.

In one human study of a GHRH analog similar to Tesamorelin, researchers reported approximately:

• 69% increase in overall GH output (AUC)

• 55% increase in mean GH pulse area

• No substantial change in pulse frequency or peak number

• Roughly 122% increase in circulating IGF-1(3)

These findings illustrate how Tesamorelin-like analogs may boost GH and IGF-1 tone without necessarily altering the basic rhythm of pulsatile secretion.

Structural Modifications and Stability

Tesamorelin differs from native GHRH via modifications at both termini, designed to improve pharmacokinetic stability.(1,4)

Key changes include:

• N-terminal acetylation

  • An acetyl group (CH₃CO–) is attached at the N-terminus

  • This modification may enhance stability and biological activity

• C-terminal trans-3-hexenoic acid group

  • An omega-amino acid modification (trans-3-hexenoic acid) is added at the C-terminus

  • This is believed to further reinforce resistance to enzymatic breakdown

Chemically, Tesamorelin is described as:
N-(trans-3-hexenoyl)-[Tyr¹]hGRF(1–44)NH₂ acetate(4)

Chemical Makeup

• Molecular Formula: C₂₂₁H₃₆₆N₇₂O₆₇S

• Molecular Weight: 5136 g/mol

• Other Names: (3E)-hex-3-enoylsomatoliberin

Research and Experimental Findings

1. Tesamorelin and Lipodystrophy / Visceral Fat

Lipodystrophy is characterized by abnormal fat distribution, often combining loss of subcutaneous fat (lipoatrophy) with excess visceral or ectopic fat (lipohypertrophy). These patterns are typically associated with:

• Insulin resistance

• Elevated triglycerides and cholesterol

• Unfavorable cardiometabolic risk markers(2,6,11)

In two pooled phase III, double-blind, placebo-controlled trials involving 806 HIV-positive subjects with excess abdominal fat, Tesamorelin was studied over 26 weeks, with a 26-week extension.(6)

Study design and outcomes:

• Initial 26 weeks:

  • 543 subjects received Tesamorelin

  • 263 subjects received placebo

• Extension phase:

  • Responders were re-randomized to continue Tesamorelin or switch to placebo

Key findings after 26 weeks:

• Approximate 15.4% reduction in visceral adipose tissue (VAT) in the Tesamorelin group

• Significant reductions in triglycerides and improvements in certain cholesterol parameters compared to placebo(6)

Additional analyses and reviews suggest Tesamorelin may reduce visceral fat by up to ~25% in lipodystrophy models, highlighting its potential impact on central adiposity in specific clinical populations.(11)

2. Tesamorelin and Non-Alcoholic Fatty Liver Disease (NAFLD) in HIV

HIV infection with antiretroviral therapy is frequently associated with hepatic steatosis, and non-alcoholic fatty liver disease (NAFLD) can be present in a substantial proportion of these individuals.(5,7)

In one multicenter randomized trial, 61 HIV-positive subjects with elevated hepatic fat fraction (HFF) were assigned Tesamorelin or placebo for 12 months.(5)

Reported observations:

• After 12 months, approximately 35% of Tesamorelin-treated subjects achieved an HFF reduction to below 5%, versus only 4% in the placebo group(5)

• Improvements in liver fat appeared independent of significant changes in fasting glucose, suggesting no major worsening of glycemic control in this context(5,7)

These results support the hypothesis that Tesamorelin may reduce hepatic steatosis in carefully selected HIV-associated NAFLD models.

3. Tesamorelin and Muscle Tissue Composition

A secondary analysis using computed tomography (CT) imaging examined the effects of Tesamorelin on muscle quality and composition in adults with HIV.(10)

Findings suggested that Tesamorelin:

• Increased muscle area and/or improved density in key muscle groups, including:

  • Rectus abdominis

  • Psoas major

  • Paraspinal muscles

• Reduced intermuscular fat within these muscle compartments

Statistically, these changes in muscle area, density, or intramuscular fat content were significantly different when compared with placebo, indicating a potential favorable shift in body composition, not just VAT reduction.(10)

4. Tesamorelin and Liver Fat / Fibrosis (Ongoing & Completed Studies)

Additional clinical work has investigated Tesamorelin’s effect on liver fat and histology in HIV-positive subjects with NAFLD.(5,7)

• NCT02196831 is a registered trial designed to explore Tesamorelin’s impact on liver histology and fibrosis progression in this context.(7)

• Published data to date suggest reductions in hepatic fat fraction and improvement in some steatosis-related parameters, with ongoing analysis of longer-term histologic outcomes.(5)

5. Tesamorelin and Cognition (Ongoing Research)

A separate clinical study was initiated to assess Tesamorelin’s potential effects on neurocognitive performance in aging HIV-infected individuals with mild cognitive impairment.(8)

Study design highlights:

• Approximately 100 subjects aged ≥40 years

• Daily Tesamorelin for 6 months, followed by a 6-month washout, then another 6-month exposure

• Primary outcome: change in Global Deficit Score (GDS) at 6 and 12 months(8)

At the time of the cited source, results were still pending, and final cognitive outcomes remained under investigation.

6. Tesamorelin and Insulin / Type 2 Diabetes

To examine whether Tesamorelin might adversely affect glycemic control, a randomized, placebo-controlled trial evaluated 53 subjects with type 2 diabetes over 12 weeks.(9)

Key metabolic readouts included:

• Fasting glucose

• Glycosylated hemoglobin (HbA1c)

• Overall diabetes control metrics

The study found:

• No significant worsening of fasting glucose

• No meaningful change in HbA1c

• No major differences in overall diabetes control between Tesamorelin and placebo groups(9)

These data suggest that, within the conditions studied, Tesamorelin did not significantly impair insulin sensitivity or short-term glycemic control in subjects with pre-existing type 2 diabetes.

Research-Use Only Disclaimer

Tesamorelin from OptiBuild Peptides is supplied strictly for laboratory, scientific, and in-vitro research purposes only.
It is not intended for human or veterinary use, medical therapy, or diagnostic procedures.
All purchasers must follow our Terms and Conditions and comply with all applicable regulations.

References

1. Clinical and Research Information on Drug-Induced Liver Injury. Tesamorelin. NIDDK; updated 2018 Oct 20.

2. Spooner LM, Olin JL. Tesamorelin: a GHRF analog for HIV-associated lipodystrophy. Ann Pharmacother. 2012;46(2):240–247.

3. Stanley TL, et al. Effects of a GHRH analog on GH pulsatility and insulin sensitivity in healthy men. J Clin Endocrinol Metab. 2011;96(1):150–158.

4. Ferdinandi ES, et al. Non-clinical pharmacology and safety evaluation of TH9507 (Tesamorelin). Basic Clin Pharmacol Toxicol. 2007;100(1):49–58.

5. Stanley TL, et al. Effects of Tesamorelin on NAFLD in HIV: randomized, double-blind trial. Lancet HIV. 2019;6(12):e821–e830.

6. Falutz J, et al. Tesamorelin in HIV-infected patients with excess abdominal fat: pooled phase 3 analysis. J Clin Endocrinol Metab. 2010;95(9):4291–4304.

7. ClinicalTrials.gov. Tesamorelin Effects on Liver Fat and Histology in HIV. NCT02196831.

8. ClinicalTrials.gov. Phase II trial of Tesamorelin for cognition in aging HIV-infected persons. NCT02572323.

9. Clemmons DR, Miller S, Mamputu JC. Safety and metabolic effects of Tesamorelin in type 2 diabetes. PLoS One. 2017;12(6):e0179538.

10. Adrian S, et al. Tesamorelin decreases muscle fat and increases muscle area in adults with HIV. J Frailty Aging. 2019;8(3):154–159.

11. Sivakumar T, et al. Growth hormone axis treatments for HIV-associated lipodystrophy: systematic review of placebo-controlled trials. HIV Med. 2011;12(8):453–462.