Encyclopedia

Tesamorelin is an FDA-approved synthetic analog of the full 44-amino-acid growth-hormone-releasing hormone (GHRH), marketed as Egrifta. It is approved specifically to reduce excess visceral abdominal fat in HIV-infected adults with lipodystrophy. Unlike exogenous growth hormone, it stimulates the pituitary's own pulsatile GH release via the GHRH receptor.

Tesamorelin is GHRH(1-44) modified with a trans-3-hexenoic acid group at the N-terminal tyrosine, which confers resistance to DPP-IV enzymatic degradation and extends its short native half-life. It was FDA-approved in November 2010 (Egrifta) for reduction of excess abdominal fat in HIV-positive adults with lipodystrophy, based on a pivotal phase III trial (Falutz et al., NEJM 2007, n=412) showing a 15.2% reduction in visceral adipose tissue, an 81% increase in IGF-1, and improvements in triglycerides and cholesterol ratio at 26 weeks. Newer formulations (Egrifta SV, approved 2019; Egrifta WR) reduce injection volume and reconstitution frequency but are not interchangeable milligram-for-milligram with the original formulation. It selectively reduces visceral fat with little effect on subcutaneous fat or body weight, and its effect reverses if treatment is stopped.

Mechanism of Action

Binds the GHRH receptor (GHRHR) on pituitary somatotrophs, activating the Gs-alpha/adenylate cyclase/cAMP pathway to stimulate pulsatile GH synthesis and release. This raises hepatic IGF-1 production, which drives preferential lipolysis of visceral adipose tissue.