Tesamorelin

Tesamorelin is a synthetic analog of growth hormone-releasing hormone (GHRH) that has been modified for improved stability and potency. It is FDA-approved under the brand name Egrifta for the treatment of excess abdominal fat (lipodystrophy) in HIV-positive patients receiving antiretroviral therapy.

Unlike synthetic human growth hormone (HGH), which directly provides exogenous GH, tesamorelin works by stimulating the pituitary gland to produce and release the body's own growth hormone in a natural pulsatile pattern. This approach is considered safer and more physiological than exogenous GH administration, as it preserves the body's natural feedback mechanisms.

Tesamorelin has gained significant popularity in the anti-aging and peptide therapy communities for its ability to reduce visceral fat, improve body composition, and support overall metabolic health — benefits that extend well beyond its original FDA-approved indication.

Tesamorelin mimics the action of natural GHRH:

Pituitary stimulation: Tesamorelin binds to GHRH receptors on somatotroph cells in the anterior pituitary gland, triggering the synthesis and secretion of growth hormone. Importantly, this occurs in a pulsatile fashion that mirrors the body's natural GH release pattern.

Preserved feedback loop: Because tesamorelin works through the body's natural GH axis, the normal feedback mechanisms (including somatostatin inhibition and IGF-1 feedback) remain intact. This means GH levels increase but are still regulated, reducing the risk of supraphysiological GH levels that occur with exogenous HGH injection.

Visceral fat reduction: The growth hormone released in response to tesamorelin promotes lipolysis (fat breakdown), particularly in visceral adipose tissue (the metabolically dangerous fat surrounding internal organs). Clinical trials consistently show significant reductions in trunk fat with tesamorelin treatment.

Metabolic improvements: Elevated GH levels support improved lipid profiles (reduced triglycerides, improved cholesterol ratios), enhanced insulin sensitivity in some contexts, and improved body composition (reduced fat mass with preservation or increase of lean mass).

Cognitive effects: Emerging research suggests tesamorelin may have cognitive benefits. A study in healthy older adults showed improved executive function and verbal memory with tesamorelin treatment, potentially related to GH/IGF-1 signaling in the brain.

HIV lipodystrophy trials (FDA approval basis): Two Phase 3 trials demonstrated that tesamorelin 2 mg daily reduced trunk fat by approximately 15-18% compared to placebo over 26 weeks. This reduction was maintained with continued treatment.

Visceral fat reduction: MRI studies showed an average reduction of 15-20% in visceral adipose tissue area, with some patients achieving reductions exceeding 25%. Subcutaneous fat was relatively less affected, indicating preferential visceral fat loss.

IGF-1 increase: Tesamorelin consistently elevates IGF-1 levels by approximately 50-100% from baseline, indicating effective GH axis stimulation.

Cognitive function (non-HIV): A 20-week randomized controlled trial in healthy older adults (ages 55-87) showed improvements in executive function and verbal memory with tesamorelin treatment, with effects more pronounced in those with mild cognitive impairment (Baker et al., 2012).

NASH/liver benefits: Early research suggests tesamorelin may reduce hepatic fat content and improve markers of liver inflammation, making it a potential therapeutic option for non-alcoholic fatty liver disease.

FDA-approved dose: 2 mg subcutaneously once daily (for HIV lipodystrophy).

Off-label use: Many peptide therapy practitioners prescribe 1 mg daily for anti-aging and body composition purposes, as this dose has shown meaningful GH elevation with potentially fewer side effects.

Timing: Best administered in the evening before bed or in the morning on an empty stomach, as food intake (particularly fats and carbohydrates) can blunt the GH response. Many practitioners recommend injecting at bedtime to complement the body's natural nocturnal GH surge.

Cycle considerations: Common protocols involve 3-6 months on, followed by a break of 1-3 months. Some practitioners advocate for continuous use with periodic monitoring of IGF-1 levels to guide dosing.

Important: Tesamorelin requires a functioning pituitary gland to be effective. It will not work in individuals with pituitary damage or diseases that impair GH production at the pituitary level.

Common side effects: Injection site reactions (redness, itching, swelling) in up to 10% of users, arthralgia (joint pain) due to elevated GH/IGF-1, paresthesia (tingling/numbness) in hands or feet, peripheral edema (water retention), and headache.

GH-related effects: Carpal tunnel syndrome symptoms, fluid retention, and joint stiffness can occur as GH levels increase. These effects are typically dose-related and may resolve with dose reduction.

Monitoring recommended: Regular monitoring of IGF-1 levels (to ensure they remain in normal range), fasting glucose/HbA1c (GH can impair glucose tolerance), and cancer screening (GH promotes cell proliferation).

Contraindications: Active malignancy, disruption of the hypothalamic-pituitary axis (head trauma, hypophysectomy), hypersensitivity to tesamorelin or mannitol, and pregnancy (Category X — known fetal harm).