Tesamorelin

Chemical Identity

Property	Value
Chemical Formula	C221H366N72O67S1
Molecular Weight	5136 Da
CAS Number	218949-48-5
Peptide Class	GHRH Analog (44 amino acids)
Route	SC injection

Structure

Tesamorelin (Egrifta) is a synthetic analog of human growth hormone-releasing hormone (GHRH) with a trans-3-hexenoyl group attached to the N-terminus. This lipid modification stabilizes the peptide against DPP-4 degradation while maintaining full GHRH receptor agonist activity.

Mechanism of Action

Tesamorelin binds GHRH receptors on pituitary somatotrophs, stimulating pulsatile growth hormone release in a physiological pattern. This increases hepatic IGF-1 production and promotes lipolysis, particularly visceral adipose tissue. The N-terminal modification prevents rapid enzymatic degradation.

Clinical Applications

• HIV-associated lipodystrophy: Reduction of excess visceral abdominal fat (Egrifta)
• Excess visceral adipose tissue: FDA-approved for HIV patients on antiretroviral therapy
• Cognitive function: Under investigation for mild cognitive impairment
• Body composition: Reduction in trunk fat

Pharmacokinetics

• Half-life: 26-38 minutes
• Tmax: 15 minutes (SC)
• Bioavailability: ~100% (SC)
• Metabolism: DPP-4 (resistant), proteolytic degradation
• Dosing: 2 mg SC daily
• Route: SC injection (abdomen)

Safety and Side Effects

Injection site reactions (erythema, pruritus), arthralgia, pain, peripheral edema, and glucose intolerance. IGF-1 monitoring recommended. Contraindicated in pituitary tumors and active malignancy.

References

• Falutz, J., et al. (2007). Tesamorelin for HIV lipodystrophy. New England Journal of Medicine, 357, 2137-2146.
• Falutz, J., et al. (2010). Long-term tesamorelin for HIV lipodystrophy. Clinical Infectious Diseases, 50, 605-612.