Tesamorelin

Overview

Tesamorelin (Egrifta / Egrifta SV) is a stabilized analog of human GHRH(1-44) with a trans-3-hexenoic acid moiety at the N-terminus that protects against protease degradation. FDA-approved in November 2010 for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy, it is the only FDA-approved GHRH analog for this indication. Off-label use for general body composition and visceral fat reduction in non-HIV populations is common but outside the approved label.

Mechanism of Action

Tesamorelin binds to GHRH receptors on anterior pituitary somatotrophs, stimulating pulsatile endogenous growth hormone release and downstream IGF-1 elevation, which preferentially reduces visceral adipose tissue. The N-terminal trans-3-hexenoic acid modification confers resistance to dipeptidyl peptidase IV and extends plasma half-life (~26-38 min) compared with native GHRH(1-44) and sermorelin (GRF 1-29).

Research Summary

FDA approval (NDA 022505) was based on two Phase 3 trials reported by Falutz et al. (NEJM, 2007) and the pooled 52-week safety extension, showing ~15-18% reduction in visceral adipose tissue with improved triglycerides in HIV patients with abdominal fat accumulation. Stanley et al. (JAMA, 2014) demonstrated concurrent reductions in visceral fat and liver fat (NAFLD). Baker et al. (Arch Neurol, 2012) reported favorable effects on executive function in older adults with and without mild cognitive impairment at 1 mg/day for 20 weeks.

Dosing Information

Reported Side Effects

• Injection site reactions — erythema, pruritus, hematoma (most common)
• Arthralgia and extremity pain
• Peripheral edema
• Myalgia
• Paresthesia
• Elevated IGF-1; GH-axis changes may theoretically support growth of occult malignancy

Research References

• Metabolic effects of a growth hormone-releasing factor in patients with HIV (Falutz et al., NEJM) (2007)
• Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial (Stanley et al., JAMA) (2014)
• Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults (Baker et al., Arch Neurol) (2012)