Tesamorelin

Introduction
Tesamorelin is a synthetic growth hormone releasing hormone analogue used in the treatment of visceral adiposity in human immunodeficiency virus (HIV) infected patients with lipodystrophy. Tesamorelin is given subcutaneously and has major effects on glucose and lipid metabolism, but has not been linked to serum aminotransferase elevations during therapy or to instances of clinically apparent acute liver injury.

Background
Tesamorelin (tes” a moe rel’ in) is a synthetic 44 amino acid polypeptide analogue of growth hormone releasing hormone (GHRH). The N terminal portion of the molecule has been modified to improve its stability and pharmacokinetics in comparison to native GHRH. Tesamorelin activates GHRH receptors in the pituitary which leads to synthesis and release of growth hormone that acts on multiple cells of the body including hepatocytes where it stimulates production of insulin like growth factor-1 (IGF-1). IGF-1 mediates many of the effects of growth hormone, which in the liver include growth, inhibition of programmed cell death, glucose update and lipolysis. Serum IGF-1 levels tend to be low in patients with obesity, diabetes and particularly in those with lipodystrophy. Tesamorelin was evaluated and found to be effective in decreasing visceral adiposity in patients with lipodystrophy associated with antiretroviral therapy of human immunodeficiency virus (HIV) infection. Tesamorelin was approved for use in the United States as therapy to reduce excess abdominal fat in HIV-infected patients with antiviral therapy-related lipodystrophy in 2010. Tesamorelin is also being evaluated as therapy of insulin resistance, obesity and nonalcoholic fatty liver. Tesamorelin is available in solution in vials of 1 mg/mL under the brand name Egrifta. The recommended dose is 2 mg daily given by subcutaneous injection. Side effects are not common but can include injection site reactions, itching, arthralgia, myalgia and peripheral edema. Tesamorelin raises IGF-1 levels and monitoring for elevations during therapy is recommended. Potential, rare adverse events include stimulation of malignant tumor growth, glucose intolerance, diabetes and hypersensitivity reactions.

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