Tesamorelin (Egrifta): GHRH Analogue for HIV Lipodystrophy

Synthetic GHRH analogue. FDA-approved for HIV-associated visceral-fat excess; reduces abdominal fat by ~18%.

✅ Approved

Full name
Tesamorelin acetate
Class
Growth hormone-releasing hormone (GHRH) analogue
Half-life
~26 minutes (effect outlasts)
Route
Subcutaneous daily
Brand names
Egrifta / Egrifta SV (Theratechnologies)
Regulatory status
FDA-approved 2010 for HIV-associated lipodystrophy

What it is

Tesamorelin is a 44-amino-acid GHRH analogue stabilised by an N-terminal trans-3-hexenoyl modification. It binds the pituitary GHRH receptor, triggering endogenous, pulsatile GH release that preserves normal physiologic feedback — distinct from exogenous GH therapy.

How it works

The GHRH receptor on somatotroph cells couples to cAMP and calcium signalling, driving GH exocytosis. Because release is pulsatile and sensitive to somatostatin/IGF-1 feedback, IGF-1 rises within the normal physiologic range rather than being pushed supraphysiologically.

The preferential reduction of visceral adipose tissue in HIV lipodystrophy reflects GH’s lipolytic action on visceral depots. Effects on liver fat have driven interest in NAFLD indications.

What the research shows

Pivotal trials in HIV-associated lipodystrophy and exploratory studies in NAFLD.

Falutz J. et al. (2007) — Phase 3 HIV lipodystrophy

Falutz J. et al., N Engl J Med 2007;357:2359–2370. 👥 Human studies

412 HIV patients with abdominal fat accumulation randomised 2:1 to tesamorelin 2 mg daily or placebo for 26 weeks.

Visceral adipose tissue reduced 15–20% vs ~2% placebo. Triglycerides improved; subcutaneous fat was minimally affected.

Limitations: Effect lost within 6 months of stopping treatment; IGF-1 rises can be clinically relevant.

Stanley TL et al. (2019) — NAFLD in HIV

Stanley T.L. et al., Lancet HIV 2019;6:e821–e830. 👥 Human studies

61 HIV patients with NAFLD received tesamorelin or placebo for 12 months.

Hepatic fat fraction decreased 32% vs 4.5% placebo; fibrosis progression was reduced.

Limitations: Small; HIV-specific population; transient glucose effects.

Safety and limitations

Well tolerated in HIV lipodystrophy trials. Common: injection-site reactions, arthralgias, transient paresthesia. Monitor fasting glucose — elevations are small but consistent with GH physiology.

Contra-indicated in active malignancy; not for use after organ transplant or in pituitary tumour.

Sources

  1. Falutz J. et al. N Engl J Med 2007;357:2359–2370. PubMed
  2. Stanley T.L. et al. Lancet HIV 2019;6:e821–e830. PubMed

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