Tesamorelin (Egrifta)

Tesamorelin is a synthetic analog of growth hormone-releasing hormone (GHRH) that consists of all 44 amino acids of human GHRH with the addition of a trans-3-hexenoic acid group at the tyrosine residue. This modification increases stability against enzymatic degradation while maintaining full biological activity at the GHRH receptor. FDA-approved under the brand name Egrifta for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy, tesamorelin represents one of the few GHRH analogs to achieve regulatory approval. It stimulates physiological, pulsatile growth hormone release.

Tesamorelin acts through the GHRH receptor on pituitary somatotrophs: **GHRH Receptor Activation:** Tesamorelin binds to GHRH receptors on pituitary somatotroph cells, activating adenylyl cyclase and increasing intracellular cAMP. This triggers GH gene transcription and GH release. **Pulsatile GH Release:** Unlike exogenous GH administration, tesamorelin stimulates physiological pulsatile GH release, which better maintains GH receptor sensitivity and mimics natural GH secretion patterns. **IGF-1 Increase:** The GH released in response to tesamorelin stimulates hepatic IGF-1 production, which mediates many of GH's metabolic effects including effects on body composition. **Visceral Fat Reduction:** Clinical trials demonstrated significant reduction in visceral adipose tissue (VAT) in HIV-associated lipodystrophy patients, likely through GH's lipolytic effects and improvements in lipid metabolism.