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MUSCLE GROWTHFDA ApprovedGHRH ANALOGLIPODYSTROPHYFDA APPROVED

Tesamorelin

Also known as: Egrifta · TH9507

18.9k views/week 478 citations 0 edits Updated 4/6/2026

Tesamorelin is an FDA-approved synthetic analog of human growth hormone-releasing hormone (GHRH), conjugated with trans-3-hexenoic acid to improve stability. It is approved under the brand name Egrifta for treatment of HIV-associated lipodystrophy — excess abdominal fat accumulation caused by antiretroviral therapy.

STRUCTURE

Molecular Composition

FORMULA
C₂₂₁H₃₆₆N₇₂O₆₇S
MOL. WEIGHT
5135.93 Da
SEQUENCE LENGTH
44 amino acids
CAS NUMBER
218949-48-9
FDA STATUS
Approved (Egrifta)
HALF-LIFE
~26 min (SQ)
AMINO ACID CHAIN VISUALIZATION
Y
Tyr
GHRH N-terminal start
NH-CO
A
Ala
DPP-IV protection
NH-CO
D
Asp
GHRHR binding
NH-CO
A
Ala
helical stability
NH-CO
I
Ile
hydrophobic core
NH-CO
F
Phe
receptor contact
NH-CO
T
trans-3-hexenoic (N-term)
protease resistance mod
SEQUENCEY-A-D-A-I-F-T
MECHANISMS

How It Works

🧬
Full-length GHRH(1-44) Receptor Agonism
Tesamorelin is the only GHRH analogue that retains the full 44-amino-acid sequence of endogenous GHRH, providing maximum receptor occupancy and GHRHR binding kinetics. The trans-3-hexenoic acid N-terminal modification prevents DPP-IV cleavage at the first peptide bond (Ala²) — the primary cause of rapid degradation in native GHRH and sermorelin.
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Selective Visceral Fat Reduction
Phase 3 HIV lipodystrophy trials demonstrated a mean 18% reduction in visceral adipose tissue (VAT) after 26 weeks — without significant changes in subcutaneous fat. This visceral selectivity is mechanistically linked to higher GHS-R and IGF-1R density in visceral adipocytes and the direct lipolytic effects of GH on visceral fat depots.
💡
Pulsatile GH Preservation
Like all GHRH analogues, tesamorelin stimulates GH through the intact pituitary feedback axis. Somatostatin feedback is preserved, preventing chronic supraphysiological IGF-1 levels. The short 26-minute half-life ensures GH is released in pulses rather than continuously — maintaining long-term somatotroph health and receptor sensitivity.
❤️
Metabolic & Cardiovascular Benefits
Beyond fat loss, tesamorelin trials showed improvements in triglycerides, total cholesterol, and carotid intima-media thickness (CIMT) — a marker of cardiovascular risk. These benefits correlate with visceral fat reduction and GH-driven improvements in lipid metabolism rather than direct vascular effects of GHRH.
OVERVIEW

Research Overview

Tesamorelin was developed by Theratechnologies and received FDA approval in 2010 for HIV-associated lipodystrophy — making it the only GHRH analog with full FDA approval for human therapeutic use. The compound addresses a significant clinical need: antiretroviral drugs, particularly older NRTIs and PIs, cause characteristic visceral fat accumulation that increases cardiovascular risk and severely impacts patient quality of life.

In Phase 3 trials (LIPO-010 and LIPO-011), tesamorelin reduced visceral adipose tissue by 18–26% over 26 weeks compared to placebo. Unlike GH administration, tesamorelin preserves the pulsatile nature of GH secretion and is less likely to cause insulin resistance, making it a significantly safer approach than direct GH replacement.

Mechanism of Action

// PHYSIOLOGICAL GHRH RECEPTOR ACTIVATION

Tesamorelin is a full-length GHRH(1-44) analog that activates GHRH receptors on pituitary somatotrophs with native-like potency. The trans-3-hexenoic acid conjugation at the N-terminus protects the otherwise labile Tyr-Ala dipeptide from DPP-IV cleavage, extending half-life from ~7 minutes to ~26 minutes.

// VISCERAL ADIPOSE REDUCTION

Elevated GH signaling promotes lipolysis (fat breakdown) in adipocytes through hormone-sensitive lipase activation. Visceral fat is particularly responsive to GH-mediated lipolysis due to higher GH receptor density. GH also opposes insulin-stimulated triglyceride storage in visceral depots.

SEQUENCE

Amino Acid 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 (44 AA, trans-3-hexenoic acid conjugated)
DOSAGE

Dosage & Administration

INJECTABLE (SUBCUTANEOUS) — FDA-APPROVED (HIV LIPODYSTROPHY)
DOSE
2 mg
FREQUENCY
Once daily at bedtime
NOTES
FDA-approved dosing for HIV-associated lipodystrophy (visceral fat accumulation). Inject into abdomen at bedtime. Supplied as lyophilized powder requiring reconstitution — use provided diluent. Rotate injection sites. Do not inject into lipodystrophic areas.
INJECTABLE (SUBCUTANEOUS) — OFF-LABEL BODY COMPOSITION
DOSE
1–2 mg
FREQUENCY
Once daily at bedtime
NOTES
Off-label use for visceral fat reduction and body composition in non-HIV adults. The bedtime injection capitalises on peak GH pulsatility during sleep. 1 mg/day is commonly used as a starting dose; 2 mg/day for the full approved effect. IGF-1 monitoring recommended for cycles beyond 12 weeks.

Tesamorelin is the only full-length GHRH(1-44) analogue to reach FDA approval. Its trans-3-hexenoic acid modification at the N-terminus prevents DPP-IV cleavage at Ala², dramatically extending its half-life while preserving full GHRHR agonism. It is specifically approved for reducing excess abdominal visceral fat in HIV patients (Egrifta, Theratechnologies) and represents the highest-evidence GHRH analogue for visceral fat reduction. Unlike HGH, it preserves pulsatility and pituitary feedback regulation.

CYCLING

Cycle Duration Guide

ON CYCLE
Continuous use approved for HIV indication; 12–26 weeks for body composition research
OFF CYCLE
No mandatory off-cycle for approved indication. Research protocols: 4–8 weeks off.

For the FDA-approved indication, tesamorelin is used continuously without formal off-cycling — similar to GLP-1 agents. For body composition research in non-HIV adults, 12–26 week cycles are used with an off-period to allow IGF-1 normalisation. Visceral fat reductions from the approved trials (mean ~18% at 26 weeks) partially reverse upon discontinuation, supporting the chronic-use model for those with ongoing visceral adiposity.

Tesamorelin is contraindicated in active malignancy, disruption of the hypothalamic-pituitary axis, and pregnancy. As with all GHRH analogues, elevated IGF-1 carries a theoretical risk of promoting pre-existing malignant cells. Monitor IGF-1 during extended use and maintain levels within normal physiological range (not supraphysiological).

Quick Reference
FORMULAC₂₂₁H₃₆₆N₇₂O₆₇S
MOL. WEIGHT5,135.93 Da
LENGTH44 amino acids
ORIGINSynthetic full-length GHRH(1-44) analog with trans-3-hexenoic acid N-terminal conjugation
HALF-LIFE~26 minutes (subcutaneous)
SOLUBILITYLyophilized powder; reconstituted in sterile water
CAS NO.218949-48-9
STATUSFDA Approved
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TAGS
GHRH analoglipodystrophyFDA approvedvisceral fatgrowth hormoneHIV