Tesamorelin Peptide

Tesamorelin is a synthetic polypeptide consisting of 44 amino acids and is structurally analogous to growth hormone-releasing hormone (GHRH). A modification at the N-terminus distinguishes it from native GHRH, and this alteration is suggested by researchers to enhance the peptide’s stability.(1)

Tesamorelin has been studied for its mechanism of action, which is proposed to mirror that of GHRH by interacting with GHRH receptors located in the anterior pituitary gland. This interaction may stimulate the production and secretion of growth hormone. Growth hormone, in turn, may act on various cell types, including hepatocytes in the liver, promoting the systemic production of insulin-like growth factor-1 (IGF-1). Additionally, growth hormone may also stimulate local IGF-1 synthesis within different tissues throughout the body.(1)

Overview

IGF-1 is widely regarded as a primary anabolic mediator of growth hormone, potentially supporting cellular growth while inhibiting programmed cell death.(1) In contrast, growth hormone itself is often described as lipolytic, promoting the breakdown of fat in specific adipose regions, including abdominal and visceral fat deposits. Tesamorelin is proposed to stimulate the release of both growth hormone and IGF-1 through interaction with GHRH receptors located on anterior pituitary cells. This interaction may induce conformational changes in the receptor, initiating intracellular signalling pathways.

One proposed mechanism involves the stimulation of cyclic adenosine monophosphate (cAMP) production via activation of the enzyme adenylate cyclase, which converts ATP into cAMP. Elevated cAMP levels may then activate protein kinase A (PKA), a key signalling enzyme responsible for phosphorylating target proteins and triggering downstream cellular responses. Through this cAMP–PKA signalling cascade, Tesamorelin may promote the secretion of growth hormone from somatotroph cells in the pituitary gland. Research suggests that Tesamorelin exposure may result in an approximate 69% increase in overall growth hormone levels (measured by area under the curve) and a 55% increase in mean pulse amplitude, without significantly altering pulse frequency or peak levels. Additionally, IGF-1 levels have been reported to increase by approximately 122%.(3)

Structural modifications at both the N-terminus and C-terminus of the Tesamorelin molecule are believed to enhance its stability and resistance to enzymatic degradation compared to native GHRH.(4) Specifically, the C-terminus is modified by the addition of a trans-3-hexenoic acid group—an omega-amino acid modification that may improve resistance to enzymatic breakdown. At the N-terminus, the attachment of an acetyl group (CH₃CO–) is thought to further enhance molecular stability and biological activity. As a result of these targeted modifications, Tesamorelin is chemically designated as N-(trans-3-hexenoyl)-[Tyr¹]hGRF(1–44)NH₂ acetate, reflecting its altered peptide structure.

Chemical Makeup
  • Molecular Formula: C221H366N72O67S
  • Molecular Weight: 5136 g/mol
  • Other Known Titles: (3E)-hex-3-enoylsomatoliberin
Research and Clinical Studies
Tesamorelin Peptide and Lipodystrophy

Lipodystrophy refers to abnormal or pathological patterns of fat distribution and metabolism within the body. It is characterised by the uneven allocation of fat stores, with loss of fat (lipoatrophy) in certain regions and excessive accumulation (lipohypertrophy) in others. This irregular distribution is often associated with adverse metabolic consequences, including insulin resistance and elevated levels of cholesterol and triglycerides. Experimental models of lipodystrophy have also been reported to exhibit reduced levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In this context, researchers investigating Tesamorelin have suggested that the peptide may exert beneficial effects on lipid metabolism, particularly in models displaying lipodystrophic features.

For example, two phase III clinical studies(6) were conducted involving 806 subjects over an initial 26-week period, followed by a 26-week extension. All participants presented with immunodeficiency and lipodystrophy. The cohort was divided into two groups, with 543 subjects receiving Tesamorelin and 263 receiving a placebo during the first phase. After 26 weeks, the Tesamorelin group was further randomised into two subgroups: one continued treatment with Tesamorelin, while the other was switched to placebo for the extension phase. At the 26-week mark, researchers reported a significant reduction in visceral adipose tissue among the Tesamorelin-treated group, with decreases of at least 15.4%. In addition, levels of triglycerides and cholesterol were observed to be significantly lower compared to the placebo group, suggesting a potential improvement in lipid-related metabolic parameters.

Tesamorelin Peptide and Immunodeficient Fat Fractions

Researchers have suggested that severe immunodeficiency may contribute to the development of non-alcoholic fatty liver disease (NAFLD), which has been reported in approximately 40% of HIV-positive individuals in clinical settings.(7) In one study,(5) 61 subjects with HIV and elevated hepatic fat fraction (HFF) were selected to evaluate the effects of Tesamorelin. Participants were administered either Tesamorelin or a placebo over a 12-month period, with HFF levels assessed at the conclusion of the study.

After 12 months, findings indicated that 35% of subjects receiving Tesamorelin experienced a reduction in HFF to below 5%, compared to only 4% of subjects in the placebo group who showed any reduction. Notably, no significant changes in glucose levels were reported, suggesting that the observed effects on liver fat occurred without measurable impact on glucose metabolism.

Tesamorelin Peptide and Cognition

In this clinical study,(8) immunodeficient subjects presenting with mild cognitive impairment were evaluated to assess the potential effects of Tesamorelin on neurological function. A total of 100 participants, all over the age of 40, were included in the trial. The study design involved daily administration of Tesamorelin for an initial period of 6 months, followed by a 6-month phase without treatment. Tesamorelin was then reintroduced and administered once daily for an additional 6 months.

The primary outcome measure focused on changes in neurocognitive performance, assessed using the Global Deficit Score (GDS) at both 6 and 12 months. At present, the study remains ongoing, and final results have not yet been published.

Tesamorelin Peptide and Insulin

The primary objective of this study(9) was to evaluate whether Tesamorelin may influence insulin sensitivity. In this 12-week randomised clinical trial, 53 subjects with type II diabetes were enrolled and divided into three groups, each receiving either a low dose of Tesamorelin, a higher dose, or a placebo.

At the conclusion of the study, key metabolic parameters—including fasting glucose levels, glycosylated haemoglobin (HbA1c), and overall diabetes control—were assessed. The findings indicated no significant changes in these measures across any of the groups, with results appearing comparable between Tesamorelin-treated subjects and those receiving placebo.

Tesamorelin Peptide and Muscle Tissue

In a research investigation,(10) the potential effects of Tesamorelin on muscle tissue structure were assessed using computed tomography (CT) imaging. CT scanning, which combines X-ray technology with computer processing, was utilised to generate detailed visualisations of internal muscle structures.

The findings suggested a possible association between Tesamorelin exposure and improvements in muscle density and overall muscle volume. Notably, certain muscle groups—including the rectus abdominis, psoas major, and paraspinal muscles—demonstrated more pronounced changes. These included increases in muscle density and size, as well as reductions in intramuscular fat content. From a statistical standpoint, these changes were reported to be significantly different when compared to the control group receiving a placebo, indicating a potential structural impact of the peptide on muscle composition.

Tesamorelin Peptide and Visceral Fat

Visceral obesity refers to the accumulation of excess fat surrounding and within internal organs, a condition commonly observed in models of lipodystrophy—an abnormal distribution of fat tissue. This form of fat deposition is associated with a range of metabolic disturbances, including insulin resistance, where the body’s response to insulin is impaired, leading to elevated blood glucose levels. It is also linked to the development of atherosclerosis, characterised by plaque buildup within arterial walls, as well as increased levels of low-density lipoprotein (LDL) cholesterol and hyperuricemia, an excess of uric acid in the body. These associations highlight that lipodystrophy extends beyond cosmetic implications and may contribute to significant metabolic dysfunction.

In exploring potential approaches to address these challenges, Tesamorelin—a synthetic analogue of growth hormone-releasing hormone—has been proposed as a compound of interest. Research suggests that Tesamorelin may contribute to reductions in visceral fat, with some studies indicating decreases of up to approximately 25% in lipodystrophy models.(11)

Tesamorelin peptide is available for research and laboratory purposes only. Please speak to our friendly research team to find out more and for sourcing options.

References:

  1. Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Tesamorelin. [Updated 2018 Oct 20].  https://www.ncbi.nlm.nih.gov/books/NBK548730/

  2. Spooner, L. M., & Olin, J. L. (2012). Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy. The Annals of pharmacotherapy, 46(2), 240–247.   https://doi.org/10.1345/aph.1Q629

  3. Stanley TL, Chen CY, Branch KL, Makimura H, Grinspoon SK. Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men. J Clin Endocrinol Metab. 2011 Jan;96(1):150-8. doi: 10.1210/jc.2010-1587. Epub 2010 Oct 13. PMID: 20943777; PMCID: PMC3038486.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038486/

  4. Ferdinandi ES, Brazeau P, High K, Procter B, Fennell S, Dubreuil P. Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic Clin Pharmacol Toxicol. 2007 Jan;100(1):49-58. doi: 10.1111/j.1742-7843.2007.00008.x. PMID: 17214611.  https://pubmed.ncbi.nlm.nih.gov/17214611/

  5. Stanley, T. L., Fourman, L. T., Feldpausch, M. N., Purdy, J., Zheng, I., Pan, C. S., Aepfelbacher, J., Buckless, C., Tsao, A., Kellogg, A., Branch, K., Lee, H., Liu, C. Y., Corey, K. E., Chung, R. T., Torriani, M., Kleiner, D. E., Hadigan, C. M., & Grinspoon, S. K. (2019). Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. The lancet. HIV, 6(12), e821–e830.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981288/

  6. Falutz J, Mamputu JC, Potvin D, Moyle G, Soulban G, Loughrey H, Marsolais C, Turner R, Grinspoon S. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010 Sep;95(9):4291-304. doi: 10.1210/jc.2010-0490. Epub 2010 Jun 16. PMID: 20554713.   https://pubmed.ncbi.nlm.nih.gov/20554713/

  7. Tesamorelin Effects on Liver Fat and Histology in HIV.  https://clinicaltrials.gov/ct2/show/NCT02196831

  8. Phase II Trial of Tesamorelin for Cognition in Aging HIV-Infected Persons.  https://clinicaltrials.gov/ct2/show/record/NCT02572323

  9. Clemmons, D. R., Miller, S., & Mamputu, J. C. (2017). Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial. PloS one, 12(6), e0179538.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472315/

  10. Adrian S, Scherzinger A, Sanyal A, Lake JE, Falutz J, Dubé MP, Stanley T, Grinspoon S, Mamputu JC, Marsolais C, Brown TT, Erlandson KM. The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV. J Frailty Aging. 2019;8(3):154-159. doi: 10.14283/jfa.2018.45. PMID: 31237318; PMCID: PMC6766405.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766405/

  11. Sivakumar T, Mechanic O, Fehmie DA, Paul B. Growth hormone axis treatments for HIV-associated lipodystrophy: a systematic review of placebo-controlled trials. HIV Med. 2011 Sep;12(8):453-62.   doi: 10.1111/j.1468-1293.2010.00906.x. Epub 2011 Jan 25. PMID: 21265979.

Dr. Marinov

Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.

Tesamorelin Peptide