Tesamorelin

Tesamorelin is a synthetic 44-amino acid polypeptide corresponding to the full sequence of human growth hormone-releasing hormone (GHRH) with a critical N-terminal modification: attachment of a trans-3-hexenoic acid group to the N-terminus. This acylation protects the peptide from cleavage by dipeptidyl peptidase-IV (DPP-4), the primary enzyme responsible for GHRH inactivation in plasma, thereby extending its effective half-life well beyond that of native GHRH (which is degraded within 7 minutes). The modification confers stability while preserving full agonist activity at the GHRH receptor. Tesamorelin binds GHRH receptors on anterior pituitary somatotroph cells, activating the adenylate cyclase–cAMP intracellular signaling cascade that drives synthesis and pulsatile secretion of growth hormone (GH). Downstream, GH acts on hepatocytes and peripheral tissues to stimulate IGF-1 production, protein synthesis, lipolysis, and metabolic regulation. Clinical studies demonstrate that once-daily tesamorelin augments both basal and pulsatile GH secretion with a physiological pattern closely resembling endogenous GHRH stimulation. FDA-approved in 2010 (Egrifta®) for HIV-associated lipodystrophy, tesamorelin has been shown to significantly reduce visceral adipose tissue while improving metabolic parameters and lean body mass in treated patients. Investigational research has expanded to non-alcoholic fatty liver disease (NAFLD/NASH), where tesamorelin reduces hepatic fat content and markers of liver inflammation. Additional areas of study include age-related GH decline (somatopause), insulin resistance, and body composition optimization.