Tesamorelin

Tesamorelin Peptide

Tesamorelin is a synthetic polypeptide of 44 amino acids, analogous to growth hormone–releasing hormone. The N-terminus has been modified relative to native GHRH, a change researchers suggest may improve stability.

Tesamorelin has been examined for a mechanism similar to GHRH via receptors in the anterior pituitary, potentially increasing production and release of growth hormone. Growth hormone acts on several tissues, including hepatocytes, and can stimulate systemic insulin-like growth factor-1 (IGF-1) synthesis. Growth hormone may also stimulate local IGF-1 production within various tissues.

Overview

IGF-1 is cited as the main anabolic mediator of growth hormone, promoting growth and limiting programmed cell death. Growth hormone itself is described as lipolytic, encouraging fat breakdown at defined depots such as abdominal and visceral fat stores. Tesamorelin appears to stimulate growth hormone release and downstream IGF-1 by interacting with GHRH receptors in anterior pituitary cells. When Tesamorelin binds the GHRH receptor, investigators hypothesize that receptor conformation and downstream signaling may shift. It is also proposed that Tesamorelin can increase intracellular cyclic AMP in certain cells through adenylate cyclase, converting ATP to cAMP. Higher cAMP may activate protein kinase A, which relays signals to multiple targets. The combined GHRH-receptor stimulation and cAMP-PKA pathway is proposed to promote growth hormone secretion and distribution from somatotrophs. Reported findings include an estimated 69% increase in overall growth hormone exposure by AUC and a roughly 55% rise in mean pulse area, while peak or frequency of pulses showed no change. IGF-1 levels reportedly increased by about 122%.

Both peptide termini of GHRH are altered in Tesamorelin. These changes are associated with greater stability and increased resistance to enzymatic deactivation. The C-terminus carries a trans-3-hexenoyl group, a modification often referenced for protection against enzymatic breakdown. The N-terminus bears an acetyl group (CH3CO), which can enhance stability and bioactivity. Chemically, Tesamorelin is designated N-(trans-3-hexenoyl)-[Tyr1]hGHRF(1-44)NH2 acetate.

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 fat distribution and metabolism, including loss of fat from some regions and excess deposition in others. It is often associated with insulin resistance and elevated cholesterol and triglycerides. In phase III work, 806 subjects were studied over 26 weeks with a 26-week extension. One group (n=543) received Tesamorelin and the remainder placebo; after 26 weeks the cohorts were re-randomized for another 26 weeks. At week 26, Tesamorelin was associated with a significant reduction in visceral adipose tissue of at least 15.4%. Triglyceride and cholesterol levels were also significantly lower than in the placebo group.

Tesamorelin Peptide and Immunodeficient Fat Fractions

Serious immunodeficiencies may drive non-alcoholic fatty liver disease in a substantial fraction of HIV-positive subjects. In one study, 61 HIV-positive participants with high hepatic fat fraction (HFF) received Tesamorelin or placebo for 12 months. At study end, 35% of subjects on Tesamorelin showed an HFF reduction of less than 5% compared with only 4% on placebo reporting any HFF decrease. No change in glucose levels was reported.

Tesamorelin Peptide and Cognition

A clinical study in immunodeficient models with mild cognitive impairment assessed neurological outcomes. One hundred subjects older than 40 years received daily Tesamorelin for 6 months, followed by a 6-month period without peptide, then reintroduction once daily for another 6 months. The primary outcome was change in Global Deficit Score at 6 and 12 months. The trial is ongoing and final results have not been published.

Tesamorelin Peptide and Insulin

A 12-week randomized clinical study in 53 subjects with type 1 diabetes evaluated insulin sensitivity. Participants received lower-dose Tesamorelin, higher-dose Tesamorelin, or placebo. After 12 weeks, fasting glucose, HbA1c, and insulin dose were unchanged across groups, indicating no significant difference among arms.

Tesamorelin Peptide and Muscle Tissue

Computed tomography was used to evaluate structural quality of muscle after Tesamorelin. Specific muscle groups, including rectus abdominis, psoas major, and paraspinal muscles, showed notable changes. Depending on the site, density and size increased, or intramuscular fat decreased, with differences relative to placebo reaching statistical significance.

Tesamorelin Peptide and Visceral Fat

Visceral obesity is the buildup of fat around and within internal organs and is common in lipodystrophy. It is linked with insulin resistance, impaired glucose handling, and dyslipidemia. Research on Tesamorelin has suggested reductions in visceral fat of up to 25% in lipodystrophy models, highlighting a possible path for metabolic improvement.

Tesamorelin peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.

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.