Tesamorelin is a synthetic 44-amino-acid analogue of human growth-hormone-releasing hormone (hGRF/GHRH), modified at the N-terminus with a trans-3-hexenoyl group to confer resistance to dipeptidyl peptidase-4 (DPP-4) degradation. It is the only GHRH analogue to have received FDA approval as a medicinal product — marketed as Egrifta for HIV-associated lipodystrophy. Compared with the older sermorelin (which contains only residues 1-29 of native GHRH), tesamorelin retains the full 44-residue sequence and the DPP-4-stabilising modification, producing a substantially more potent and longer-lasting stimulus to endogenous GH release.
Tesamorelin binds the GHRH receptor on anterior-pituitary somatotrophs, driving pulsatile release of endogenous growth hormone. Because the upstream signal is the body's own pituitary release rather than exogenous recombinant GH, the physiologic feedback loops governing pulse architecture, somatostatin-mediated suppression and IGF-1 negative feedback remain intact — a research distinction from direct hGH administration.
The DPP-4-resistant N-terminal modification (trans-3-hexenoyl group) is the key engineering feature. Native GHRH is cleaved by DPP-4 within minutes; tesamorelin's modified backbone resists this cleavage, extending the duration of receptor activation and producing a sustained, physiologic-pattern GH pulse rather than a brief, supra-physiologic spike.
Clinical research in HIV-associated lipodystrophy (the approved indication) documented preferential reduction in visceral adipose tissue with concomitant improvements in lipid and insulin-resistance markers, accompanied by IGF-1 increases that remained within the upper end of the normal range.
The Phase 3 development programme (Falutz et al., NEJM 2007 and follow-on trials) studied tesamorelin in adults with HIV-associated lipodystrophy — a condition characterised by excess visceral adipose tissue accumulation. Over 26 weeks, tesamorelin 2 mg subcutaneous daily produced a mean reduction of approximately 18% in visceral adipose tissue mass versus placebo, with parallel improvements in lipid panels and quality-of-life measures.
The FDA approval followed in 2010 (as Egrifta). The clinical evidence base remains the deepest of any GHRH analogue.
Compared with sermorelin (GHRH 1-29, unstabilised), tesamorelin's full 44-residue sequence and DPP-4-resistant backbone produce markedly higher potency and longer duration of action. Compared with exogenous hGH, tesamorelin preserves endogenous pulse architecture and somatostatin feedback — a research feature when the experimental aim is to study GH/IGF-1 axis modulation rather than overall axis bypass.
In stack research, tesamorelin is most commonly paired with ipamorelin (a selective GHRP that acts on the parallel ghrelin-receptor pathway). The two compounds engage non-overlapping receptors and produce synergistic, amplified GH release in published research — the rationale for the Apex GH Blend.