Tesamorelin: Complete Guide

Tesamorelin is a modified form of human growth hormone-releasing hormone (GHRH 1-44). The modification — a trans-3-hexenoic acid group attached to the tyrosine at position 1 — protects the molecule from enzymatic degradation by dipeptidyl peptidase IV (DPP-IV), extending its biological half-life compared to native GHRH.

Developed by Theratechnologies Inc., tesamorelin received FDA approval in 2010 for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy — a condition characterized by abnormal fat distribution that develops as a side effect of antiretroviral therapy. It remains the only FDA-approved treatment specifically targeting visceral adipose tissue (VAT).

The distinction between tesamorelin and exogenous growth hormone (somatropin) is clinically important. Exogenous GH replaces natural production and disrupts the hypothalamic-pituitary feedback loop. Tesamorelin instead works upstream, stimulating the pituitary to release GH in its natural pulsatile pattern, preserving negative feedback mechanisms and resulting in a more physiological GH profile.

Tesamorelin binds to GHRH receptors on somatotroph cells in the anterior pituitary gland, triggering the synthesis and secretion of growth hormone. This process involves:

1. Receptor binding: Tesamorelin binds GHRH receptors (GHRHR) with similar affinity to endogenous GHRH
2. cAMP signaling: Receptor activation stimulates adenylyl cyclase, increasing intracellular cAMP
3. GH release: Elevated cAMP triggers GH release from stored secretory granules and stimulates new GH gene transcription
4. Downstream effects: Released GH acts on the liver to produce IGF-1, and directly on adipose tissue to stimulate lipolysis

The visceral fat reduction occurs primarily through GH's lipolytic effect on adipocytes. GH activates hormone-sensitive lipase in fat cells, promoting the breakdown of stored triglycerides. Visceral adipocytes are particularly responsive to GH-mediated lipolysis because they have a higher density of GH receptors compared to subcutaneous fat cells.

Visceral Fat Reduction

The pivotal Phase 3 trials (conducted in HIV-positive patients with lipodystrophy) demonstrated:

• 15–18% reduction in visceral adipose tissue (VAT) measured by CT scan at 26 weeks
• Significant reduction in trunk fat and waist circumference
• No significant change in subcutaneous abdominal fat or limb fat
• Improvements in patient-reported body image and quality of life
• Effects reversed upon discontinuation, suggesting ongoing treatment is needed

Liver Fat Reduction

Research published in The Lancet HIV found tesamorelin reduced hepatic fat fraction by 37% in HIV-positive patients with nonalcoholic fatty liver disease (NAFLD). This is noteworthy because NAFLD is increasingly common in the general population and current pharmacological options are limited.

Cognitive Function

A study published in Neurology examined tesamorelin's effects on cognitive function in older adults. Participants receiving tesamorelin showed improved executive function and verbal memory compared to placebo, with effects correlating to IGF-1 level increases. This research area is still early but has generated interest in GH-related cognitive decline.

Cardiovascular Markers

Clinical data showed improvements in triglyceride levels and total cholesterol/HDL ratios in tesamorelin-treated patients. These improvements are thought to be secondary to visceral fat reduction, as VAT is a significant driver of dyslipidemia.

The FDA-approved dosing protocol:

Parameter	Detail
Dose	2 mg daily
Route	Subcutaneous injection (abdominal area)
Timing	Once daily, preferably at the same time each day
Duration	Assessed at 26 weeks; discontinued if no improvement in VAT
Reconstitution	Each vial reconstituted with provided sterile water

In the approved formulation (Egrifta/Egrifta SV), tesamorelin comes as a lyophilized powder that is reconstituted with sterile water for injection. Use the peptide calculator for reconstitution math if working with research-grade material. For injection technique, see the injection guide.

For detailed protocols, visit the tesamorelin dosage guide.

As an FDA-approved drug, tesamorelin has the most complete safety profile of any GHRH analog. Common side effects from clinical trials include:

• Injection site reactions (25–36%): Erythema, pruritus, pain, irritation, or hemorrhage at the injection site — the most frequently reported adverse event
• Arthralgia (13%): Joint pain, likely related to elevated GH/IGF-1 levels
• Peripheral edema (6%): Fluid retention, typically mild and transient
• Myalgia (5%): Muscle pain
• Paresthesias (5%): Tingling or numbness, associated with fluid retention effects on peripheral nerves

Contraindications:

• Active malignancy — GH stimulation could theoretically promote tumor growth
• Disruption of the hypothalamic-pituitary axis (head surgery, radiation, trauma)
• Hypersensitivity to tesamorelin or mannitol
• Pregnancy

Tesamorelin may impair glucose tolerance and increase the risk of developing type 2 diabetes in predisposed individuals, as GH is a counter-regulatory hormone to insulin. Blood glucose monitoring is recommended during treatment. Read more in the tesamorelin side effects guide.

Several GHRH analogs are used in research. Here is how tesamorelin compares:

Feature	Tesamorelin	Sermorelin	CJC-1295
Structure	GHRH(1-44) + hexenoic acid	GHRH(1-29)	GHRH(1-29) + DAC/MPA
FDA approved	Yes (Egrifta)	Previously (Geref, discontinued)	No
Half-life	26 minutes	~10 minutes	~30 min (no DAC) / days (with DAC)
GH release pattern	Pulsatile	Pulsatile	Sustained (with DAC)
Clinical evidence	Phase 3 trials, FDA review	Phase 3 (historical)	Phase 2 only
Primary research use	Visceral fat, NAFLD	Anti-aging, GH deficiency	GH secretion, body composition

Tesamorelin has the strongest clinical evidence base due to its FDA approval pathway, which required large, randomized, placebo-controlled trials with rigorous safety monitoring.