Description
Summary Abstract
Tesamorelin (TH9507; GHRH(1-44)-trans-3-hexenoic acid; Egrifta®) is a synthetic 44-amino acid analog of growth hormone–releasing hormone (GHRH) conjugated at the N-terminus with a trans-3-hexenoic acid moiety, conferring resistance to dipeptidyl peptidase IV (DPP-IV) cleavage and substantially extending functional plasma half-life compared to native GHRH. It is the only FDA-approved GHRH analog in clinical use, indicated for reduction of excess abdominal fat in HIV-infected patients with lipodystrophy under the trade names Egrifta®, Egrifta SV®, and Egrifta WR™ (the weekly reconstitution formulation approved in 2025). Tesamorelin drives pulsatile growth hormone (GH) secretion from anterior pituitary somatotrophs, activating the GH/IGF-1 axis with downstream lipolytic effects on visceral adipose tissue. A substantial clinical dataset spanning metabolic, hepatic, and cognitive endpoints makes it one of the more rigorously characterized growth hormone secretagogues in current literature.
Clinical Indications
Tesamorelin has generated controlled clinical evidence across several metabolic and neurological domains:
- HIV-Associated Lipodystrophy: Falutz et al. (2007) demonstrated a 15.2% reduction in visceral adipose tissue (VAT) versus a 5.0% increase in placebo over 26 weeks (p < 0.001); pooled 52-week data show a sustained ~18% VAT reduction.
- Metabolic-Associated Steatotic Liver Disease (MASLD/NAFLD): A placebo-controlled trial found a 37–40% relative reduction in liver fat fraction, with 35% of treated patients achieving normal hepatic fat fraction (<5%) vs 4% of placebo; fibrosis progression was halted in the tesamorelin arm.
- Cognitive Function in Aging: Exploratory research has examined GH/IGF-1 axis augmentation and its relationship to executive function and working memory in aging cohorts, drawing on the hormone’s established CNS distribution.
- Body Composition in Non-HIV Populations: The VAT-reduction mechanism is under active investigation in non-HIV metabolic syndrome and abdominal obesity research contexts.
Contraindications
- Active Malignancy: Tesamorelin elevates IGF-1, which can serve as a growth factor in established tumors; use is contraindicated in the presence of active neoplastic disease.
- Hypothalamic-Pituitary Axis Disruption: Pre-existing pituitary or hypothalamic damage (e.g., post-irradiation, pituitary tumor) impairs the somatotroph response and negates the mechanism of action.
- Pregnancy: FDA Pregnancy Category X — fetal exposure to elevated IGF-1 carries teratogenic risk; tesamorelin is contraindicated throughout pregnancy.
Mechanism of Action (MOA)
Tesamorelin binds the GHRH receptor (GHRHR) on anterior pituitary somatotrophs, activating the GH/IGF-1 axis while preserving physiologic pulsatility through two principal mechanisms:
GHRHR Activation & Pulsatile GH Secretion
Tesamorelin binds GHRHR on pituitary somatotrophs, stimulating pulsatile growth hormone (GH) release. Elevated GH drives hepatic IGF-1 synthesis via the GH/IGF-1 axis. Critically, tesamorelin preserves physiologic GH pulsatility rather than inducing sustained supraphysiologic GH levels, maintaining downstream receptor sensitivity and minimizing tachyphylaxis.
Visceral Lipolysis via HSL/LPL
GH-mediated activation of hormone-sensitive lipase (HSL) and suppression of lipoprotein lipase (LPL) in visceral adipocytes drives selective lipolysis of visceral adipose tissue (VAT). The trans-3-hexenoic acid N-terminal conjugate confers DPP-IV resistance, extending functional half-life from minutes (native GHRH) to approximately 26–38 minutes for tesamorelin.
DPP-IV Resistance
Native GHRH(1-44) is rapidly cleaved by DPP-IV at the Tyr-Ala bond between positions 1 and 2. Tesamorelin replaces this N-terminal sequence with a trans-3-hexenoic acid conjugate, which is not a substrate for DPP-IV, preserving the receptor-binding N-terminus and substantially prolonging the pharmacokinetically active fraction in plasma.
Key Features & Specifications
Tesamorelin offers a distinctive pharmacological profile among GHRH analogs available for metabolic and GH-axis research:
Chemical Analysis
| Property | Specification Reference Data |
|---|---|
| Sequence | 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 + trans-3-hexenoic acid (N-terminal) |
| CAS Number | 218949-48-9 |
| Molecular Formula | C221H366N72O67S |
| Molecular Weight | ~3,357.9 g/mol |
| PubChem CID | 16132395 |
| Synonyms | TH9507; Egrifta; Egrifta SV; Egrifta WR; GHRH(1-44)-trans-3-hexenoic acid |
| Form / Variation | 5 MG Lyophilized (P-042) / 10 MG Lyophilized (P-048) |
Storage, Safety, and Handling
Storage Protocol
Lyophilized tesamorelin (pre-reconstitution) should be stored at controlled room temperature (15–30°C), protected from light and moisture. Reconstituted solution must be refrigerated at 2–8°C and used within 21 days; do not freeze the reconstituted preparation. Reconstitute with sterile water for injection or bacteriostatic water by rolling the vial gently — do not shake. Discard if the solution is cloudy, discolored, or contains visible particulates.
Handling & Compliance
Handle with standard sterile technique; use gloves and appropriate personal protective equipment (PPE) when preparing reconstituted solutions. Subcutaneous injection is the required route; no meaningful oral bioavailability exists. Tesamorelin is prohibited under WADA S2 (Peptide Hormones, Growth Factors, and Related Substances), in- and out-of-competition. Glucose metabolism monitoring (fasting plasma glucose, HbA1c) is standard practice during tesamorelin administration given the documented hazard ratio of 3.3 for new-onset diabetes mellitus in Phase III trials.