Tesamorelin/Ipamorelin Blnd 11mg/6mg

Tesamorelin (TH9507) is a synthetic 44-amino acid analog of endogenous GHRH with a molecular weight of 5135.9 Da. It was developed by Theratechnologies Inc. to overcome the inherent instability of native GHRH, which has a half-life of only 3–8 minutes due to rapid cleavage by DPP-4. [1] [2]

Key Structural Feature: A trans-3-hexenoic acid group is anchored to the N-terminal tyrosine (Tyr1), rendering the peptide resistant to DPP-4 degradation and extending the half-life to approximately 26–38 minutes. C-terminal is amidated (-NH₂). [3]

Regulatory Status:

• FDA: Approved as Egrifta SV / Egrifta WR for HIV-associated lipodystrophy (excess abdominal fat reduction). NOT indicated for weight loss. [4]
• EMA: Application withdrawn; not marketed in the EU. [6]
• WADA: Prohibited (S2 — Peptide Hormones, Growth Factors). [5]

Developer: Theratechnologies Inc. (Montreal, Canada) — originally designated TH9507.

Pharmacokinetic Highlights:

• Bioavailability: <4% (subcutaneous)
• Half-Life: ~26–38 min (SC); ~11 min (1.28 mg WR formulation)
• Route: Subcutaneous injection (abdomen)
• Standard Dose: 2 mg SC daily (Egrifta SV); 1.28 mg SC daily (Egrifta WR, bioequivalent)
• Pulsatility: Preserves natural pulsatile GH secretion (unlike rhGH)

1. Receptor Target — GHRH Receptor

Tesamorelin acts as a specific agonist for the GHRH receptor (GHRHr), a seven-transmembrane G protein-coupled receptor (GPCR) located on somatotroph cells in the anterior pituitary gland. Binding potency is comparable to endogenous GHRH. [7]

2. DPP-4 Resistance

The trans-3-hexenoic acid modification at the N-terminal Tyr1 acts as a chemical shield against DPP-4 cleavage. Native GHRH is rapidly degraded (T½ ~5 min); Tesamorelin's modification extends stability to ~26–38 min. [3]

3. Downstream Signaling Cascade

Gₛ → Adenylyl Cyclase → cAMP → PKA → Ca²⁺ Influx → GH Exocytosis:

1. Receptor activation triggers the Gₛα subunit
2. Gₛα stimulates adenylyl cyclase, converting ATP to cAMP
3. Elevated cAMP activates Protein Kinase A (PKA)
4. PKA opens voltage-gated Ca²⁺ channels → calcium influx
5. Ca²⁺ triggers exocytosis of pre-stored GH vesicles
6. Simultaneously, cAMP promotes GH gene transcription (new GH synthesis) [7]

The product supplied here is for research use only regardless of regulatory status of related formulations.

4. Selectivity

Tesamorelin is highly selective for the GHRH receptor. It does not significantly alter TSH, LH, ACTH, or Prolactin levels. Unlike GHRPs (e.g., Ipamorelin), it does not bind the ghrelin receptor. [9]

5. Cellular and Tissue-Level Effects

Adipose Tissue:

• Selectively reduces visceral adipose tissue (VAT) by ~15–18%, minimal effect on subcutaneous fat [10]
• Activates hormone-sensitive lipase (HSL), inhibits lipoprotein lipase (LPL)
• Visceral fat cells have higher GH receptor density, explaining selectivity

Hepatic (Liver):

• Reduces hepatic fat (~37% relative reduction) [11]
• Reduces de novo lipogenesis, enhances fatty acid oxidation
• Prevents progression of liver fibrosis (10.5% vs 37.5% progression, P=0.04) [11]

Musculoskeletal:

• Promotes protein synthesis, increases trunk lean mass and muscle area [12]
• Improves muscle density (myosteatosis reduction)

Nervous System:

• Improves executive function and verbal memory in MCI/aging [13]
• Increases GABA levels, modulates amyloid-beta pathways

6. Comparison with Related Molecules

7. Pharmacokinetics

Parameter	Value
Route	Subcutaneous (abdomen)
Bioavailability	<4% (SC)
Half-Life (T½)	~26–38 min (SC, 2 mg); ~11 min (1.28 mg WR)
Standard Dose	2 mg SC daily (SV); 1.28 mg SC daily (WR)
GH Pulsatility	Preserved (natural pulses, IGF-1 feedback intact)
Metabolism	Proteolytic cleavage; no formal human metabolism studies
Animal T½	21–45 min (dogs)

💊 HIV-Associated Lipodystrophy (FDA-registered)

The primary clinical application. Two pivotal Phase 3 trials (n=816) demonstrated 14–18% VAT reduction with 2 mg SC daily, with improvements in triglycerides (-12.3%), body image, and waist circumference. Reductions were maintained over 52 weeks but reversed upon discontinuation. [4] [10]

🫁 NAFLD / NASH

A 12-month RCT (n=61) in HIV-infected study subjects showed 37% hepatic fat reduction, with 35% achieving normal hepatic fat fraction (<5%). Critically, Tesamorelin prevented progression of liver fibrosis (10.5% vs 37.5% in placebo, P=0.04). [11]

🧠 Cognitive Function / MCI

In a blinded RCT (n=152) of healthy older adults and MCI study subjects, 1 mg daily for 20 weeks improved executive function (P=0.005) and global cognition (P=0.03), with IGF-1 increasing +117%. Mechanisms involve increased GABA and amyloid-beta modulation. [13]

🦴 Peripheral Nerve Regeneration

Preclinical GH models showed enhanced median nerve regeneration (axon density P<0.005, myelin thickness P<0.0001) and improved muscle re-innervation (38% vs 27.9%, P<0.02). Tesamorelin is identified as the optimal agent for human translation. [14]

❤️ Cardiovascular Risk Reduction

Reduces triglycerides and improves carotid intima-media thickness (cIMT). VAT reduction is theorized to lower atherosclerotic cardiovascular disease risk. Long-term cardiovascular outcomes remain under study. [15]

💪 Sarcopenia / Muscle Quality

Increases skeletal muscle density and area (particularly trunk region), independent of changes in muscle mass quantity. Replaces hypertrophic lipid-engorged fat cells with healthy tissue. [12]

🍬 Metabolic Syndrome / Type 2 Diabetes

A tolerability study in T2D study subjects (n=53) demonstrated neutral glucose effects — no significant changes in fasting glucose, HbA1c, or insulin response vs placebo. However, Phase 3 HIV data showed increased HbA1c risk (HR 3.3 vs placebo), warranting monitoring. [16]

Clinical Trials

Reported Tolerability Profile

Established through 800+ study subjects in Phase 3 trials. [4]

• Common (>5%): Arthralgia, injection site erythema/pruritus, pain in extremity, peripheral edema, myalgia
• Hypersensitivity: 3.6–4% (pruritus, erythema, flushing, urticaria)
• Glucose: Increased risk of HbA1c ≥6.5% (HR 3.3 vs placebo); monitor glucose
• Reproductive: Pregnancy Category X — hydrocephaly in rat offspring at 2–4x human dose; delayed skull ossification at lower doses
• Contraindications: Active malignancy, hypophysectomy/pituitary tumor, pregnancy, hypersensitivity