Egrifta (tesamorelin acetate, TH9507)
Tesamorelin is a synthetic GH secretagogue from the growth hormone releasing hormone (GHRH) family. This drug mimics the activity of endogenous GHRH. It acts on the pituitary to stimulate the pulsatile release of growth hormone, an important regulator of metabolism and body composition. GH has been shown to reduce fat mass through several actions, including inhibition of adipocyte differentiation, the stimulation of fat mobilization, and enhanced fat oxidation. Via stimulation of IGF-I, it is also an import participant in anabolism. Tesamorelin is approved in the United States for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy. In the fitness community, this drug is widely used to support muscle growth and fat loss.
In human pharmacokinetic/pharmacodynamics studies, 2 mg of tesamorelin daily for 2 weeks was shown to significantly increase serum growth hormone levels.1 2 Elevations were noted in both basal hormone secretion and total GH pulse area, with no change in the frequency of GH pulses. This is consistent with other drugs of the GHRH class. During this study, mean overnight GH secretion increased by approximately 70% (from 0.7 to 1.2 mcg/L). and GH area under the curve increased by a similar amount (from 531 to 897 mcg/L). IGF-I was also significantly increased with treatment. In this case, levels more than doubled (from 148 mcg/L to 329 mcg/L).
In prolonged human studies, the strong effect of tesamorelin on the GH/IGF-I axis persists.3 After 3 months (12 weeks) of treatment at 2 mg daily, IGF-I levels remained elevated by an average of 60% (from 110.6 ng/mL to 176.6 ng/mL). After 6 months (26 weeks), approximately half (47.4%) and one-third (35.6%) of patients still had IGF-I levels that were 2 and 3 standard deviations above normal for their age and gender, respectively. With regard to its apparent physical effects, long-term tesamorelin use was shown to significantly decrease trunk fat, total body fat mass, and waist circumference.4 At the same time, lean body mass (LBM) increased, underlining its distinct anabolic component. Serum lipids (triglycerides, and Total, LDL, and HDL Cholesterol) were also improved.
• Moderate/Strong Effect on GH and IGF-1
• Supports Anabolism
• Supports Fat Loss
• Well Studied/Tolerated
Tesamorelin was developed by Valeant Pharmaceuticals. The drug was subsequently licensed to Theratechnologies. who secured exclusive development rights to the drug. They filed a New Drug Application with the Food and Drug Administration back in October 2001. The first appearance of tesamorelin in the medical literature seemed to come roughly 3 years after, when some of its basic pharmacokinetic properties were studied in dogs.5
During the 2000s, tesamorelin was subject to an extensive series of preliminary studies, as well as Phase I, II, and III human clinical trials. The company compiled a substantive collection of favorable safety and efficacy studies on the drug. Tesamorelin was finally approved as a medication by the FDA in 2010.6 It is now sold in the United States under the Egrifta trade name, which is marketed by Serono for the treatment of lipodystrophy associated with HIV. The drug was approved in Canada in 2015 for the same application.
Tesamorelin is on the World Anti-Doping Agency’s (WADA) list of prohibited substances. Methods for detecting the misuse of this compound are available.7
Tesamorelin as a synthetic analogue of human GHRH. It is small peptide consisting of the native 44 amino-acid sequence of human GHRH, with a hydrophobic side chain that increases resistance to metabolism by the enzyme dipeptidylaminopeptidase 4 (DPP4). Tesamorelin has the chemical name N-[trans-3-Hexenoyl]-human growth hormone-releasing factor (1-44) acetate. It has a mean terminal elimination half-life of approximately 26-38 minutes.
Egrifta (tesamorelin acetate) is supplied in two multi-dose vials, each containing 1.1 mg of tesamorelin as a lyophilized powder. A diluent (sterile water for injection) is also provided. After reconstitution, this solution should be injected immediately. Non-reconstituted tesamorelin should be stored under refrigeration (36°F to 46°F, 2°C to 8°C).
This drug can also be purchased as a research compound or gray market supplement. It is typically supplied in multidose vials containing 2, 5, and 10 mg of dry lyophilized powder. This should be reconstituted with bacteriostatic water before use.
Any unused portion is often kept briefly) under refrigeration for 710 days. If reconstituted with saline, any unused portion should be discarded.
This drug should never be used during pregnancy, with active cancer, disruption of the hypothalamic-pituitary testicular axis due to hypophysectomy, hypopituitarism, pituitary tumor/surgery, head irradiation or head trauma, or a known hypersensitivity to tesamorelin or mannitol (an excipient).
Side Effects (General):
During human clinical studies, tesamorelin was well tolerated. Side effects were generally mild. Some of the most common reports involved adverse effects typically associated with other types of growth hormone therapy. These occurred in 25.6% of patients, and included water retention (edema), joint pain (arthralgias), carpal tunnel syndrome, and numbness or tingling in the extremities. Note that the incidence of GH-related side effects tends to be lower with GHRP therapy as compared to traditional hGH. This is because GH/IGF-1 release is subject to the limits of endogenous synthesis, and as such the drug is less amenable to overdosing.
During Phase III trials, no clinically meaningful mean changes were noted in liver enzymes (alkaline phosphatase), alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin. There were no clinically significant changes in thyroidstimulating hormone, luteinizing hormone, or prolactin as well.
Side Effects (Injection site):
The subcutaneous administration of this drug may cause redness, itching, pain, or lumps at the site of injection. Adverse reactions at the site of injection were common, having been reported by 24.5% of patients during Phase III clinical trials.
The recommended prescribed dose of tesamorelin acetate is 2 mg, which is injected subcutaneously once per day.
The recommended injection site is the abdomen. Injection sites should be rotated to different areas of the abdomen.
When used for physique- or performance-enhancing purposes, tesamorelin is usually given at a dose of 1-2 mg daily. This is given in one episode. Use of tesamorelin is typically characterized by a visible reduction in fat mass, and mild increases in lean body mass.
Cycles usually last 3-4 months, though programs of 6 months or longer are not uncommon. During Phase III human studies, antibody formation was reported in approximately 50% of patients receiving tesamorelin. The appearance of these antibodies had no clinically significant effects on GH release, however.
Tesamorelin (a GHRH) may be combined with a drug from the GHRP (Growth Hormone Releasing Peptides) class, such as such as GHRP-2, GHRP-6, hexarelin, ipamorelin, or MK-677. These two drug types alter GH release through distinct and complimentary mechanisms. Such combination therapy tends to produce substantial synergy with regard to GH release
Tesamorelin is available as a prescription drug in the U.S. and Canada under the Egrifta trade name. It is also sold as a “research compound” through various unregulated suppliers, and thus is widely available online. Note that the quality of gray market products can be difficult to assure.
1 Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects. Mario Gonzalez-Sales et al. J Pharmacokinet Pharmacodyn DOI 10.1007/s10928-015-9416-2
2 Effects of a Growth Hormone-Releasing Hormone Analog on Endogenous GH Pulsatility and Insulin Sensitivity in Healthy Men. Takara L. Stanley, Cindy Y. Chen, Karen L. Branch, Hideo Makimura, and Steven K. Grinspoon. J Clin Endocrinol Metab 96: 150–158, 2011
3 Endocrinologic and metabolic drugs advisory Committee. Tesamorelin (Egrifta) briefing document. NDA 22-606 May 27, 2010
4 Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK. 2014
5 Pulmonary delivery of TH9507, a growth hormone releasing factor analogue, in the dog. Jansen M, Darby 1, Abribat T, Dubreuil P, Ferdinandi ES, Hardy JG. 2004
6 FDA News Release: FDA approves Egrifta to treat Lipodystrophy in HIV patients 2010
7 Doping control analysis of selected peptide hormones using LCMS(/MS). Thevis M et al. Forensic Sci Int. 2011 Dec 10;213(1-3):35-41.