Tesamorelin

What it is

Tesamorelin (Egrifta) is a synthetic GHRH analog with structural modifications that enhance its half-life and biological activity compared to native GHRH. Specifically, tesamorelin is a 44-amino-acid peptide identical to native GHRH(1-44) with a trans-3-hexenoyl group attached to the N-terminus, which protects against DPP-4 cleavage and extends biological activity.

Tesamorelin was developed by Theratechnologies; the brand-name product Egrifta received FDA approval in 2010 for the reduction of excess abdominal fat in adults with HIV-associated lipodystrophy. This is Egrifta’s sole FDA-approved indication.

Mechanism of action

Tesamorelin binds the pituitary GHRH receptor with affinity similar to native GHRH, stimulating endogenous, pulsatile GH release. The structural modifications produce a half-life of approximately 30 minutes — substantially longer than native GHRH (about 7 minutes) but still short enough to preserve pulsatile release patterns.

Reported effects in the HIV-associated lipodystrophy trials:

• Visceral adipose reduction: elevated GH/IGF-1 promotes lipolysis preferentially in visceral fat depots, which are highly responsive to GH signaling. This is the basis for the FDA indication.

Research findings

HIV-associated lipodystrophy (Egrifta’s FDA-approved indication): the pivotal Phase III trials demonstrated mean visceral adipose tissue (VAT) reductions of 15–18% over 26 weeks, with no significant change in subcutaneous fat. Continued therapy maintained the benefit; discontinuation led to gradual return toward baseline.

Side effects and contraindications

Reported side effects of tesamorelin include:

• Joint discomfort and arthralgia — reflects fluid retention in synovial tissue from elevated GH
• Peripheral edema — particularly in lower extremities
• Paresthesias — tingling in hands and feet, sometimes carpal tunnel-like symptoms
• Glucose intolerance — GH antagonizes insulin action and can worsen insulin resistance
• Injection site reactions
• Headache and fatigue in some patients

Contraindicated in:

• Active malignancy
• Pregnancy and breastfeeding
• Pituitary disease
• Severe diabetic retinopathy
• Uncontrolled diabetes (relative contraindication; may be considered with very careful glucose monitoring)

What we don’t yet know

Tesamorelin (Egrifta) is FDA-approved only for the reduction of excess abdominal fat in adults with HIV-associated lipodystrophy. Its effectiveness and safety for other uses have not been established, and long-term cardiovascular outcomes are not well characterized.