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Research Monograph

Tesamorelin Acetate (trans-3-hexenoic acid-GHRH(1-44)NH₂)

Also Known AsTH9507 · Egrifta · Egrifta SV · trans-3-hexenoic acid modified GHRH

Molecular Weight5135.86 g/mol
Discovered2003
Citations4 peer-reviewed
Research Areas4 domains
Background

Tesamorelin was developed by Theratechnologies Inc. (Montreal, Canada) as a stabilized analog of human GHRH(1-44). The trans-3-hexenoic acid modification at the N-terminus confers resistance to dipeptidyl peptidase-IV (DPP-IV) cleavage, which normally inactivates native GHRH within minutes. FDA-approved in 2010 (Egrifta) for reduction of excess abdominal fat in HIV-infected patients with lipodystrophy.

Amino Acid Sequencehex-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH₂ (hex = trans-3-hexenoic acid)
Mechanisms of Action

How Tesamorelin Works

01

GHRH Receptor Agonism (Stabilized)

Tesamorelin binds the GHRH receptor on pituitary somatotrophs with affinity comparable to native GHRH(1-44). The trans-3-hexenoic acid N-terminal modification blocks DPP-IV cleavage, extending the functional half-life from ~7 minutes (native GHRH) to ~26 minutes. This activates the cAMP/PKA cascade, stimulating GH synthesis and pulsatile release.

GHRHRDPP-IV resistancecAMP/PKApituitary somatotrophs
02

Visceral Adipose Tissue Reduction

The GH released by tesamorelin stimulation activates hepatic and adipocyte GH receptors, promoting lipolysis via hormone-sensitive lipase activation and suppression of lipoprotein lipase. GH preferentially mobilizes visceral adipose tissue (VAT) due to higher GH receptor density in visceral vs. subcutaneous depots. This selectivity is preserved when GH is released pulsatilely.

GH receptor (adipocyte)hormone-sensitive lipaselipoprotein lipasevisceral adipose tissue
03

Hepatic Lipid Metabolism

Tesamorelin-stimulated GH release reduces intrahepatic lipid content by enhancing hepatic fatty acid oxidation and VLDL secretion. Phase III data in HIV lipodystrophy showed significant reduction in liver fat fraction measured by MRI. Emerging research extends this to non-alcoholic fatty liver disease (NAFLD) independent of HIV status.

hepatic GH receptorfatty acid oxidationVLDL secretionintrahepatic lipid
Evidence-Graded Research Areas

Published Research

Strong
Moderate
Emerging
Preclinical

HIV-Associated Lipodystrophy

Strong

Phase III randomized controlled trials (LIPO-010 and LIPO-011) demonstrated that tesamorelin 2mg daily reduced visceral adipose tissue by 15-18% vs. placebo over 26 weeks in HIV+ patients with lipodystrophy. Effects were sustained at 52 weeks with continued treatment. Trunk fat, waist circumference, and patient-reported body image all improved significantly. This evidence led to FDA approval in 2010.

Non-Alcoholic Fatty Liver Disease (NAFLD/NASH)

Strong

A randomized controlled trial in HIV+ patients with NAFLD demonstrated that tesamorelin significantly reduced hepatic fat fraction (measured by MR spectroscopy), with 35% of treated patients achieving resolution of NAFLD vs. 4% placebo. Gene expression analysis showed reduced hepatic de novo lipogenesis and fibrogenesis pathways. Studies in non-HIV NAFLD are ongoing.

Cognitive Function in Aging

Moderate

A randomized placebo-controlled trial in older adults with mild cognitive impairment (MCI) or healthy cognition demonstrated that tesamorelin improved executive function (Trails B) and verbal memory over 20 weeks. Effects correlated with increased IGF-1 levels and were preferentially observed in APOE4 non-carriers. This suggests a link between the GH/IGF-1 axis and cognitive aging.

Body Composition in Obesity

Moderate

Tesamorelin reduces visceral fat while preserving subcutaneous and peripheral fat, a selectivity profile that distinguishes it from caloric restriction (which reduces both). Studies show reductions in trunk fat are not accompanied by limb fat loss, addressing a key concern in populations where peripheral fat preservation is desired (e.g., HIV lipodystrophy).

Safety Profile

Tesamorelin has extensive Phase III clinical trial safety data and post-marketing surveillance from its FDA-approved use. Common adverse effects include injection site reactions (erythema, pruritus, pain), arthralgia, myalgia, peripheral edema, and transient hyperglycemia. IGF-1 elevation above age-adjusted normal occurs in some patients and requires monitoring. Tesamorelin is contraindicated in patients with active malignancy (as GH/IGF-1 axis stimulation is theoretically mitogenic) and during pregnancy. Long-term safety data (up to 2 years) shows a stable adverse event profile.

Handling & Storage

Reconstitute with provided sterile water or bacteriostatic water. Direct gentle stream along vial wall — do not shake. Store reconstituted solution at 2-8°C and use within 14 days. Lyophilized powder stable at 2-8°C (refrigerated) or -20°C for extended storage. Protect from light. Tesamorelin is a 44-amino-acid peptide — handle with care to avoid denaturation.

References & Citations

Peer-Reviewed Literature

  1. 1

    Metabolic effects of a growth hormone-releasing factor in patients with HIV

    Falutz J, Allas S, Blot K, et al.

    New England Journal of Medicine, 2007PubMed 18003957DOI
  2. 2

    Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension

    Falutz J, Potvin D, Mamputu JC, et al.

    Journal of Acquired Immune Deficiency Syndromes, 2010PubMed 20535215DOI
  3. 3

    Relationship of IGF-1 and IGF-binding proteins to disease severity and glycemia in nonalcoholic fatty liver disease

    Stanley TL, Fourman LT, Zheng I, et al.

    Journal of Clinical Endocrinology and Metabolism, 2021PubMed 33547468DOI
  4. 4

    Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial

    Baker LD, Barsness SM, Borber S, et al.

    Archives of Neurology, 2012PubMed 23229046DOI
Frequently Asked Questions

Tesamorelin FAQ

What is Tesamorelin?

Tesamorelin is a synthetic analog of human growth hormone-releasing hormone (GHRH 1-44) with a trans-3-hexenoic acid modification that protects it from DPP-IV enzymatic degradation. It was FDA-approved in 2010 (brand name Egrifta) for reducing excess abdominal fat in HIV-infected patients with lipodystrophy, making it the only FDA-approved GHRH analog for a metabolic indication.

How does Tesamorelin differ from Sermorelin?

Both are GHRH receptor agonists, but they differ in key ways. Sermorelin is the native GHRH(1-29) fragment with a ~12-minute half-life. Tesamorelin is the full-length GHRH(1-44) with an N-terminal trans-3-hexenoic acid modification that extends its half-life to ~26 minutes by blocking DPP-IV cleavage. Tesamorelin has Phase III clinical trial data and FDA approval; Sermorelin has older clinical data from its discontinued Geref approval.

Is Tesamorelin FDA approved?

Yes. Tesamorelin (Egrifta) received FDA approval in November 2010 for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy. Egrifta SV (a single-vial reformulation) was approved in 2019. It is the only FDA-approved therapy specifically indicated for HIV-associated visceral adipose accumulation.

How should Tesamorelin be stored?

Lyophilized Tesamorelin should be stored at 2-8°C (refrigerated) per the FDA label, or at -20°C for extended storage of research-grade material. Once reconstituted, store at 2-8°C and use within 14 days. Protect from light. Do not freeze reconstituted solution.

What is the purity of G26x Peptides Tesamorelin?

Our Tesamorelin is 99%+ purity, independently verified by Janoshik Analytical with a full Certificate of Analysis (COA) available for each batch. It is supplied as 10mg lyophilized powder manufactured under GMP-adjacent conditions.

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Disclaimer: This monograph is provided for educational and research purposes only. G26x Peptides products are sold exclusively as research chemicals. They are not intended for human consumption, therapeutic use, or as dietary supplements. All research should be conducted in compliance with applicable laws and institutional review board protocols. Information presented here is sourced from published peer-reviewed literature and does not constitute medical advice.