In Plain English:
Tesamorelin (brand name Egrifta) is a synthetic copy of the full 44-amino-acid growth hormone-releasing hormone (GHRH) your hypothalamus produces, plus a trans-3-hexenoic acid group that makes it roughly 4–5× more resistant to enzymatic breakdown than the natural version. Rather than injecting growth hormone directly, it tells your pituitary gland to release its own GH in pulses — exactly as nature intended — so the somatostatin feedback loop stays intact and keeps GH from going dangerously high. It is the only FDA-approved treatment for HIV-associated lipodystrophy (excess belly fat from antiretroviral drugs), and researchers are exploring it for fatty liver disease, metabolic syndrome, and age-related cognitive decline.
Research Maturity
Extensive Human (112 PubMed publications; includes 3 Phase 3 RCTs (N=870 combined)+ Studies)
Focus
Body Composition
Metabolic Health
Origin
Full-length synthetic analogue of human hypothalamic GHRH (hGRF 1-44), with a trans-3-hexenoic acid moiety added to the N-terminus for protease resistance. Developed by Theratechnologies (Montreal) and FDA-approved in November 2010 (NDA 022505) for reduction of excess abdominal fat in HIV-infected adults with lipodystrophy. The F8 re-formulation (Egrifta SV) was approved in 2019. CAS 218949-48-5.
Mechanism
Binds GHRH receptor (GHRHR) on anterior pituitary somatotroph cells, coupling to Gs protein → adenylate cyclase activation → cAMP elevation → PKA activation and IP3-mediated intracellular Ca²⁺ release → pulsatile GH synthesis and secretion. Elevated GH drives hepatic IGF-1 production. IGF-1 and GH together exert direct lipolytic effects on visceral adipocytes (HSL activation, reduced de novo lipogenesis), preferentially targeting intra-abdominal fat depots while largely sparing subcutaneous fat. Somatostatin counter-regulation remains fully intact, preventing pathological GH excess.
Outcome
Primary: visceral adipose tissue volume by CT scan (cm³). Secondary: waist circumference (cm), trunk fat by DXA, serum IGF-1 and GH AUC, hepatic fat fraction by MRS, fasting lipids (triglycerides, TC:HDL ratio), insulin sensitivity (HOMA-IR), body image distress scores, cognitive composite scores (MCI populations).
