Tesamorelin (Egrifta) — GHRH Analog — Growth Hormone

FDA-approved GHRH analog for HIV-associated lipodystrophy. Stimulates natural GH secretion with favorable safety profile.

Overview

Tesamorelin (Egrifta) is a synthetic analog of growth hormone-releasing hormone (GHRH) consisting of the 44-amino-acid sequence of human GHRH with a trans-3-hexenoic acid modification at the N-terminus. FDA-approved in 2010 for the reduction of excess abdominal fat (lipodystrophy) in HIV-infected patients with lipodystrophy, tesamorelin is the first and only GHRH analog approved for clinical use in the United States. In pivotal Phase 3 trials, tesamorelin 2 mg daily subcutaneous injection reduced trunk fat by 15-18% over 26 weeks while modestly increasing lean body mass and improving triglycerides. Unlike exogenous growth hormone, tesamorelin works by stimulating the patient's own pituitary gland to release endogenous GH in a pulsatile, physiologic manner. This preserves the natural GH feedback loop and produces lower IGF-1 elevations compared to direct GH administration, potentially reducing the risks associated with supraphysiologic GH levels. Tesamorelin does not significantly affect glucose metabolism, HbA1c, or insulin resistance in clinical trials — a notable advantage over exogenous GH which can worsen insulin sensitivity. Off-label, tesamorelin has gained popularity in the anti-aging and optimization medicine space as a GH secretagogue with a cleaner safety profile than GH itself.

Indications

  • FDA-approved: Reduction of excess abdominal fat in HIV-lipodystrophy
  • Off-label: Growth hormone optimization in aging/anti-aging medicine
  • Off-label: Body composition improvement
  • Investigational: MASH/NASH (liver fat reduction)

Mechanism of Action

Tesamorelin binds GHRH receptors on anterior pituitary somatotrophs, stimulating endogenous GH synthesis and secretion

Dosing

CompoundDoseFrequencyNotes
Tesamorelin2 mgOnce dailyFDA-approved dose for HIV-lipodystrophy
Tesamorelin1 mgOnce dailyLower dose used off-label for GH optimization

Evidence Grade

GRADE A

Safety & Contraindications

  • Injection site reactions: erythema, pruritus, pain (most common adverse effect)
  • Arthralgia, myalgia, peripheral edema (GH-related effects)
  • Paresthesias and carpal tunnel syndrome possible
  • Contraindicated with active malignancy (GH may promote tumor growth)
  • Hypersensitivity reactions (rare but reported)
  • Fat loss reverses upon discontinuation
  • IGF-1 elevation — monitor to avoid supraphysiologic levels