Tesamorelin

Tesamorelin is a GHRH analog with a trans-3-hexenoic acid modification at Tyr1 that makes it resistant to dipeptidyl peptidase-IV (DPP-IV) degradation, extending its plasma half-life compared to native GHRH. It binds to GHRH receptors on the anterior pituitary, stimulating synthesis and pulsatile release of growth hormone. This leads to elevated IGF-1 levels and downstream metabolic effects including lipolysis (fat breakdown), particularly affecting visceral adipose tissue. The preferential reduction of visceral fat is thought to relate to the higher density of GH receptors in visceral compared to subcutaneous adipose tissue.

Tesamorelin (Egrifta) is a synthetic growth hormone-releasing hormone (GHRH) analog FDA-approved for reducing excess abdominal fat in HIV-infected patients with lipodystrophy. Phase 3 trials demonstrated significant reductions in visceral adipose tissue (VAT) of 15-18% compared to placebo, with improvements in trunk fat and patient-reported body image. The peptide stimulates pulsatile GH release while maintaining the physiological feedback axis. Unlike exogenous GH, tesamorelin preserves natural GH regulation. Studies also show improvements in lipid profiles and potential cognitive benefits, though off-label use for general body composition remains less studied.