Overview

Tesamorelin is a synthetic Growth Hormone Releasing Hormone (GHRH) analog that was FDA-approved in 2010 under the brand name Egrifta for the treatment of HIV-associated lipodystrophy, specifically excess abdominal fat (visceral adipose tissue).

It remains one of the only FDA-approved peptides that directly stimulates growth hormone release, giving it a unique regulatory standing in the peptide landscape.

Key Characteristics

Origin: Synthetic GHRH analog with trans-3-hexenoic acid modification
Classification: Growth Hormone Releasing Hormone analog
FDA Status: Approved for HIV lipodystrophy (Egrifta)
Unique Feature: Selective visceral fat reduction
Advantage: Preserves/increases lean mass while reducing fat

The Visceral Fat Problem

Visceral adipose tissue (VAT) is particularly dangerous:

Surrounds internal organs
Linked to cardiovascular disease
Associated with insulin resistance
Increases inflammatory markers
More metabolically active than subcutaneous fat

Tesamorelin is one of few compounds shown to specifically target this dangerous fat depot.

Mechanism

Primary Mechanisms

1. GHRH Receptor Binding

Like other GHRH analogs, tesamorelin:

Binds to GHRH receptors on pituitary somatotrophs
Activates adenylyl cyclase pathway
Increases cAMP
Triggers GH release

2. Pulsatile GH Stimulation

Unlike synthetic GH:

Maintains natural pulsatile secretion pattern
Works with body's feedback systems
Doesn't suppress endogenous production
More physiological approach

3. IGF-1 Elevation

The released GH leads to:

Hepatic IGF-1 production
Systemic anabolic effects
Lipolysis activation
Protein synthesis enhancement

4. Targeted Lipolysis

Tesamorelin particularly affects visceral fat:

Increases lipolysis in abdominal adipocytes
Reduces trunk fat
Preserves peripheral fat distribution
May preferentially target VAT receptors

Research

Research Note: Tesamorelin has robust clinical trial data supporting its efficacy and safety, particularly for HIV lipodystrophy.

HIV Lipodystrophy (FDA Approved)

CONFIRM & DEFINE Trials

Phase 3 trials demonstrated:

15-18% reduction in trunk fat at 26 weeks
Maintained reduction with continued treatment
Improved body image and patient satisfaction
No worsening of glucose metabolism

Statistical Outcomes

Trunk fat reduced by ~1 kg (15%)
Visceral adipose tissue reduced by 15-17%
Lean body mass preserved or increased
Benefits maintained over 52+ weeks

Beyond HIV: Off-Label Research

General Visceral Fat Reduction

Studies in non-HIV populations suggest:

Similar efficacy for VAT reduction
Benefits for metabolic syndrome
Potential cardiovascular risk reduction
Improved insulin sensitivity

Cognitive Function (2025)

Emerging research indicates:

Potential neuroprotective effects
Improved cognitive scores in trials
May benefit brain health via IGF-1
Research ongoing in neurodegenerative disease

NAFLD/NASH

Non-alcoholic fatty liver disease studies show:

Reduced liver fat content
Improved liver enzymes
Potential hepatoprotective effects
Active area of research

Comparison to Other GH Therapies

| Feature | Tesamorelin | Synthetic GH | CJC-1295 | |---------|-------------|--------------|----------| | FDA Approved | Yes | Yes | No | | VAT Reduction | Excellent | Good | Good | | Pulsatile Release | Yes | No | Yes | | IGF-1 Increase | Moderate | High | Moderate | | Side Effect Profile | Favorable | More extensive | Favorable |

Dosing

Disclaimer: Tesamorelin is FDA-approved for HIV lipodystrophy only. Off-label use should be discussed with a healthcare provider. The following information is for reference only.

Research Protocols

Protocol	Dose	Frequency	Duration
FDA Approved (HIV)	2 mg	Once daily	Long-term
Off-Label (Wellness)	1-2 mg	Once daily	12-24 weeks
Conservative Start	1 mg	Once daily	4 weeks, then assess
Cycling Protocol	2 mg	Once daily	12 weeks on, 4 weeks off

Administration Notes

Timing

Once daily, preferably at same time
Can be morning or evening
Some prefer pre-bed to mimic natural GH rhythm
Empty stomach enhances absorption

Injection Technique

Subcutaneous injection (abdomen preferred)
Rotate injection sites
Avoid areas of lipodystrophy
Room temperature medication before injecting

Long-Term Use

FDA trials extended to 52+ weeks
Discontinuation leads to gradual return of fat
Consider cycling to maintain sensitivity
Monitor IGF-1 levels periodically

Reconstitution

Comes as lyophilized powder
Mix with provided diluent (0.4% carboxymethylcellulose sterile water)
Roll vial gently - do not shake
Use immediately after mixing (Egrifta)
Research preparations: use bacteriostatic water, refrigerate

Pharmacokinetics

Absorption

Subcutaneous: Rapid absorption
Peak GH levels: 15-45 minutes
Bioavailability: High

Distribution

Acts primarily at pituitary
Systemic effects through GH/IGF-1
Does not accumulate

Metabolism

Metabolized by peptidases
Trans-hexenoic acid modification provides stability
No CYP450 interactions

Elimination

Half-life: 26-38 minutes (peptide)
GH effects last several hours
Daily dosing maintains effects

Safety

Known Side Effects

Common (>5%)

Injection site reactions (erythema, pruritus)
Arthralgia (joint pain)
Peripheral edema
Paresthesias (tingling)
Myalgia (muscle pain)

Less Common (1-5%)

Carpal tunnel syndrome
Headache
Nausea
Skin rash

Generally Well-Tolerated

Side effects often mild and transient
Many resolve with continued use
Dose reduction can help

Contraindications

Absolute Contraindications:

Disruption of hypothalamic-pituitary axis (tumor, surgery, radiation)
Active malignancy
Pregnancy
Hypersensitivity to tesamorelin or mannitol

Relative Contraindications:

History of malignancy
Diabetic retinopathy
Uncontrolled diabetes

Cancer Warning: Tesamorelin increases IGF-1, which may theoretically promote tumor growth. Those with active malignancy or recent cancer history should not use this medication.

Drug Interactions

Monitor closely with:

Diabetes medications (may affect glucose)
Cortisol replacement therapy
Other GH secretagogues

Generally safe with:

HIV antiretroviral medications
Most common medications

Monitoring

Baseline Assessments

IGF-1 level
Fasting glucose and HbA1c
Lipid panel
Body composition (DEXA if available)
CT scan for visceral fat (clinical studies)

During Treatment

IGF-1 every 3-6 months
Fasting glucose periodically
Body measurements/composition
Side effect assessment

Long-Term Monitoring

Annual malignancy screening
Continued metabolic monitoring
Treatment efficacy assessment

Regulatory

Current Status

| Region | Status | |--------|--------| | United States | FDA-approved (Egrifta) for HIV lipodystrophy | | Canada | Approved | | WADA | Prohibited (S2 category) | | Off-Label | Widely used in wellness medicine |

Legal Considerations

Prescription medication in approved indications
Off-label prescribing legally permitted
Insurance coverage limited to HIV lipodystrophy
Research chemical versions available

Clinical Outlook

Tesamorelin has significant potential beyond HIV:

Studies ongoing for general obesity
NAFLD/NASH potential indication
Cognitive benefits being explored
May see expanded FDA indications
Growing use in longevity medicine

References

[1] Falutz J, et al.. Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine (2007)

[2] Falutz J, et al.. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation. Journal of Acquired Immune Deficiency Syndromes (2010)

[3] Stanley TL, et al.. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV. Lancet HIV (2019)

[4] FDA. Egrifta (tesamorelin) Prescribing Information. Food and Drug Administration (2020)

[5] Longevity Medicine Research. GHRH Analogs for Visceral Fat Reduction: Beyond HIV. Obesity Reviews (2025)