Tesamorelin

Potential Benefits of Tesamorelin

• Promotes fat loss [1-9]
• Improves cognitive function [10-19]
• Improves lipid profile [1, 9, 20-23]
• Improves liver health [24-26]
• Lowers blood sugar levels [9, 27]
• Lowers the risk of cardiovascular disease [1, 21, 28]
• Treats nerve injury [29]

What is Tesamorelin?

Tesamorelin is an FDA-approved drug for lipodystrophy, a medical condition characterized by an abnormal distribution of body fat. This small molecule (known as peptides) is a synthetic analog of growth hormone–releasing factor, which means that it stimulates the pituitary gland to secrete growth hormone (GH). This mechanism is thought to play an integral role in body fat reduction since direct GH administration has fat-burning effects.

How Tesamorelin Works?

Tesamorelin stimulates the synthesis and release of GH by acting on the pituitary cells in the brain. The increase in GH also increases the levels of insulin-like growth factor (IGF-1). This in turn stimulates muscle growth and fat loss.

Chemical Structure of Tesamorelin

Research on Tesamorelin

Promotes Fat Loss

Fat reduction is the major benefit of tesamorelin. In fact, the US Food and Drug Administration approved tesamorelin last November 2010 for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy. Several lines of evidence clearly support this fat-burning effect:

1. In HIV patients with central fat accumulation, subcutaneous injection of tesamorelin at a dose of 2 mg was generally well tolerated and resulted in sustained decrease in visceral adipose tissue (active component of total body fat). [1]
2. A 2010 study published in the Journal of Acquired Immune Deficiency Syndromes found that tesamorelin reduced visceral fat (body fat stored within the abdominal cavity) by approximately 18% and improved body image distress in HIV-infected patients with central fat accumulation. [2]
3. A 2011 study published in HIV/AIDS – Research and Palliative Care has shown that tesamorelin is safe and effective in reducing central fat accumulation among HIV-infected patients.[3]
4. In HIV patients with abdominal adiposity, tesamorelin reduced visceral adipose tissue by increasing adiponectin, a protein that breaks down fat. [4]
5. In patients with HIV-related lipodystrophy, 52 weeks of tesamorelin treatment reduced abdominal fat. [5]
6. A 2015 study published in PLoS One Journal found that patients with baseline metabolic syndrome, elevated triglyceride levels, or white race were most likely to experience reductions in visceral adipose tissue following 6 months of tesamorelin treatment. [6]
7. In HIV-infected patients with excess abdominal fat, treatment with tesamorelin reduced visceral adipose tissue and maintained the reduction for up to 52 weeks. [7]
8. In HIV-infected patients with abdominal fat accumulation, daily tesamorelin treatment for 26 weeks decreased visceral fat by 15.2% compared to placebo. [8]
9. In HIV-infected patients receiving tesamorelin, reduction in visceral adipose tissue was accompanied by improvement in metabolic profile. [9]

Improves Cognitive Function

Growth hormone–releasing hormone (GHRH) such as tesamorelin has potent effect on brain function. Studies show that this “cognitive enhancer” may benefit people with age-related memory problems and those suffering from chronic, progressive mental deterioration:

1. In older adults with memory impairment, short-term tesamorelin administration improved executive function and verbal memory. [10]
2. Daily subcutaneous injections of tesamorelin for 20 weeks improved executive function, verbal memory, and visual memory in both adults with mild cognitive impairment and healthy older adults. [11]
3. In patients with mild cognitive impairment, tesamorelin administration at a dose of 1mg/day for 10 weeks improved various areas of cognition. [12]
4. A 2012 study published in Nature Reviews Endocrinology found that tesamorelin administration in patients with age-related cognitive impairment significantly improved memory and thinking skills. [13]
5. In adults with mild cognitive impairment, daily subcutaneous injections of tesamorelin increased GH levels and improved executive function and verbal memory. [14-15]
6. In normal older adults and adults with mild cognitive impairment, tesamorelin administration for 5 months demonstrated favorable effects on cognition. [16]
7. Self-administration of tesamorelin at 1 mg 30 minutes before bedtime slowed cognitive decline in older adults. [17]
8. An ongoing Phase II trial of tesamorelin for cognition in aging HIV-infected persons shows promising results with the tesamorelin-treated group exhibiting improvement in neurocognitive performance. [18]
9. In adults with mild cognitive impairment, administration of daily subcutaneous injections of tesamorelin significantly increased the levels of gamma-Aminobutyric acid (GABA), a neurotransmitter that facilitates brain cell communication. [19]

Improves Lipid Profile

The ability of tesamorelin to improve lipid profile can be attributed to its fat-burning effect and GH-boosting properties. High-quality studies support its beneficial effect on triglycerides, total cholesterol, low-density lipoprotein (bad cholesterol), and high-density lipoprotein (good cholesterol):

1. In HIV patients with abdominal fat accumulation, subcutaneous injection of tesamorelin at a dose of 2 mg significantly improved triglycerides and total cholesterol levels. [1]
2. The administration of tesamorelin in HIV-infected patients resulted in greater reduction in triglycerides compared to placebo treatment. [9]
3. Treatment of type 2 diabetic patients with tesamorelin for 12 weeks significantly reduced total cholesterol and low-density lipoprotein. [20]
4. In HIV-infected patients with excess abdominal fat, tesamorelin treatment increased the levels of high-density lipoprotein. [21]
5. In patients with HIV, a daily subcutaneous injection of tesamorelin resulted in decreased visceral fat and improved lipid profiles. [22-23]

Improves Liver Health

Studies also show that tesamorelin may benefit liver function through various important mechanisms:

1. In HIV-infected men and women with hepatic steatosis (accumulation of fat in the liver), treatment with tesamorelin for 12 months significantly reduced liver fat. [24]
2. In HIV-infected patients with abdominal obesity who received tesamorelin, a clinically significant reduction in body fat was associated with improved liver enzymes. [25]
3. In obese subjects with reduced GH, 12 months of tesamorelin treatment led to a significantly greater increase in phosphocreatine, a substance that protects the liver from low levels of oxygen and impaired blood flow. [26]

Lowers Blood Sugar Levels

Clinical trials also show that tesamorelin can bring down high blood sugar levels by promoting fat loss:

1. The administration of tesamorelin in HIV-infected patients did not only promote abdominal fat loss but also reduce blood sugar levels after 52 weeks of treatment. [9]
2. Tesamorelin treatment for 26 weeks also reduced blood sugar levels in HIV-infected patients with excess abdominal fat. [27]

Lowers the Risk of Cardiovascular Disease

Evidence suggests that tesamorelin can help reduce the risk of cardiovascular diseases by improving various health parameters such as triglyceride levels and total cholesterol levels. [1] Tesamorelin also has the ability to raise the levels of high-density lipoprotein (good cholesterol). [21] An increase in HDL cholesterol is associated with significant cardiovascular disease risk reduction. [28]

Treats Nerve Injury

Nerve injury is one of the most debilitating medical conditions and perhaps one of the most difficult to treat as it can lead to permanent impairment in motor and sensory function of the affected area. Research, however, suggests that growth hormone-based therapies such as tesamorelin treatment can speed up the rate of healing of damaged nerves. [29]

Associated Side Effects of Tesamorelin

Tesamorelin side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on tesamorelin. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of tesamorelin. Despite this, it was listed as a side effect associated with tesamorelin even though these associated side effects are very uncommon.

Side effects associated with tesamorelin may include the following:

• Difficulty breathing
• Dizziness
• Elevations in blood sugar levels
• Fast heartbeat
• Hives
• Irritation or itching
• Joint pain
• Night sweats
• Numbness
• Rash
• Swelling of the face and throat
• Vomiting

References

1. Falutz J, Allas S, Mamputu JC, et al. Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS. 2008;22(14):1719-28.
2. Falutz J, Potvin D, Mamputu JC, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. J Acquir Immune DeficSyndr. 2010;53(3):311-22.
3. Bedimo R. Growth hormone and tesamorelin in the management of HIV-associated lipodystrophy. HIV AIDS (Auckl). 2011;3:69–79. doi:10.2147/HIV.S14561.
4. Stanley TL, Falutz J, Mamputu JC, Soulban G, Potvin D, Grinspoon SK. Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: relationship with visceral adipose reduction. AIDS. 2011;25(10):1281-8.
5. Available from http://i-base.info/htb/2092.
6. Mangili A, Falutz J, Mamputu JC, Stepanians M, Hayward B. Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat. PLoS One. 2015;10(10):e0140358. Published 2015 Oct 12. doi:10.1371/journal.pone.0140358.
7. Falutz J, Mamputu JC, Potvin D, et al. 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 ClinEndocrinolMetab. 2010;95(9):4291-304.
8. Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-70.
9. Stanley TL, Falutz J, Marsolais C, Morin J, Soulban G, Mamputu JC, et al. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis. 2012;54:1642–1651.
10. Available from https://www.alzheimersanddementia.com/article/S1552-5260(11)01582-2/abstract.
11. Baker LD, Barsness SM, Borson S, et al. Effects of growth hormone–releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Arch Neurol. 2012;69(11):1420-9.
12. Available from https://clinicaltrials.gov/ct2/show/NCT02553603.
13. Mclarnon A. Neuroendocrinology: Tesamorelin can improve cognitive function. Nat Rev Endocrinol. 2012;8(10):568.
14. Available from https://www.healio.com/psychiatry/alzheimers-disease-dementia/news/print/endocrine-today/%7B9a3378b6-43ea-46c6-8d81-330a0bec5175%7D/growth-hormone-releasing-hormone-had-positive-effect-on-cognition.
15. Vitiello MV, Moe KE, Merriam GR, Mazzoni G, Buchner DH, Schwartz RS. Growth hormone releasing hormone improves the cognition of healthy older adults. Neurobiol Aging. 2006;27:318-323.
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17. Baker, L. D. et al. Effects of growthhormone-releasing hormone on cognitive function in adultswith mild cognitive impairment on healthy older adults.Arch. Neurol. doi:10.1001/archneurol.2012.1970.
18. Available from https://clinicaltrials.gov/ct2/show/NCT02572323.
19. Friedman SD, Baker LD, Borson S, et al. Growth hormone-releasing hormone effects on brain γ-aminobutyric acid levels in mild cognitive impairment and healthy aging. JAMA Neurol. 2013;70(7):883-890. doi:10.1001/jamaneurol.2013.1425.
20. Clemmons DR, Miller S, Mamputu JC. 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. 2017;12(6):e0179538. Published 2017 Jun 15. doi:10.1371/journal.pone.0179538.
21. Maggi P, Di biagio A, Rusconi S, et al. Cardiovascular risk and dyslipidemia among persons living with HIV: a review. BMC Infect Dis. 2017;17(1):551.
22. Available from https://www.nejm.org/doi/full/10.1056/NEJMoa072375.
23. Stanley TL, Falutz J, Marsolais C, Morin J, Soulban G, Mamputu JC, Assaad H, Turner R, Grinspoon SK. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis. 2012 Jun;54(11):1642-51. doi: 10.1093/cid/cis251. Epub 2012 Apr 10. PMID: 22495074; PMCID: PMC3348954.
24. Available from https://clinicaltrials.gov/ct2/show/NCT02196831.
25. Fourman LT, Czerwonka N, Feldpausch MN, et al. Visceral fat reduction with tesamorelin is associated with improved liver enzymes in HIV. AIDS. 2017;31(16):2253–2259. doi:10.1097/QAD.0000000000001614.
26. Miller K, Halow J, Koretsky AP. Phosphocreatine protects transgenic mouse liver expressing creatine kinase from hypoxia and ischemia. Am J Physiol. 1993;265(6 Pt 1):C1544-51.
27. Spooner LM, Olin JL. Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy. Ann Pharmacother. 2012;46(2):240-7.
28. Mahdy Ali K, Wonnerth A, Huber K, Wojta J. Cardiovascular disease risk reduction by raising HDL cholesterol–current therapies and future opportunities. Br J Pharmacol. 2012;167(6):1177–1194. doi:10.1111/j.1476-5381.2012.02081.x.
29. Tuffaha SH, Singh P, Budihardjo JD, et al. Therapeutic augmentation of the growth hormone axis to improve outcomes following peripheral nerve injury. Expert OpinTher Targets. 2016;20(10):1259-65.