💊 GHRH Analog • VAT Reduction

Tesamorelin (TH9507)

Synthetic GHRH analogue that reduces visceral adipose tissue by ~15-20% in HIV-associated lipodystrophy. Stimulates pulsatile GH release while preserving physiologic feedback. ✓ FDA Approved (EGRIFTA)

Length 44 AA MW ~5135.9 Da CAS 218949-48-5

⚡ Executive Summary

Tesamorelin is a GHRH analogue that reduces visceral adipose tissue (VAT) by ~15–20% over 26–52 weeks in HIV-associated lipodystrophy while largely sparing subcutaneous fat. Effects extend to modest liver-fat reductions and better triglycerides in responders. Unlike exogenous GH, it preserves physiologic feedback and did NOT worsen glycemic control in T2D trials.

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01 Overview 02 Properties 03 Mechanism 04 Outcomes 05 Comparison 06 FAQ 📋

Overview

💊 What is Tesamorelin?

Tesamorelin is a stabilized 44-amino-acid GHRH analogue (brand name EGRIFTA) that binds the GHRH receptor to restore physiologic GH pulses.

A trans-3-hexenoyl group on Tyr¹ confers partial resistance to DPP-IV cleavage, improving exposure relative to native GHRH.

🎯 Primary Indication

• ✓ HIV-associated lipodystrophy — visceral fat reduction
• ✓ FDA approved — only peptide for this use
• ✓ Liver benefits — reduces hepatic steatosis

💡

Why GHRH vs direct GH? Unlike exogenous GH, a GHRH analogue preserves hypothalamic-pituitary feedback, allowing IGF-1–mediated self-limiting control. This explains why tesamorelin reduces VAT while generally sparing subcutaneous fat and with fewer glucose-metabolism penalties than direct GH.

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Entity Properties

Aliases	Tesamorelin, TH9507, EGRIFTA / EGRIFTA SV
Family	GHRH analogue → GHRH receptor → pulsatile GH → hepatic IGF-1
Sequence	44-AA analogue of GHRH(1-44) with N-terminal trans-3-hexenoyl on Tyr¹
Molecular Weight	~5135.9 Da (free base); ~5579 Da (acetate salt)
CAS Number	218949-48-5 (free base); 901758-09-6 (acetate)
Half-Life	~8-38 min (formulation-dependent); short but GH pulse outlasts
Bioavailability	<4% (consistent with peptide degradation)
Diluent	Sterile Water for Injection (per EGRIFTA SV labeling)
Dosing	2 mg vial + 0.5 mL → 4 mg/mL; dose 1.4 mg (0.35 mL) SC once daily
Storage	Room temp (20-25°C); use immediately after reconstitution

⚠️

Critical storage note: Unlike most peptides, reconstituted Tesamorelin should be stored at room temperature and used immediately. Do NOT refrigerate or freeze the solution — it can gel at cold temperatures. See our Tesamorelin Storage Guide for details.

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Mechanism of Action

🧠 Signaling Pathway

Tesamorelin binds the GHRH receptor on pituitary somatotrophs, triggering pulsatile GH release. This increases hepatic IGF-1 production, which drives lipid mobilization preferentially from visceral adipose depots.

Tesamorelin GHRH Analog → GHRH-R Pituitary → GH Pulses Physiologic → ↑ IGF-1 Hepatic → ↓ VAT Lipid Mobilization

🛡️ DPP-IV Resistance

The trans-3-hexenoyl modification on Tyr¹ provides partial resistance to DPP-IV cleavage — the enzyme that rapidly degrades native GHRH. This improves exposure and bioactivity.

⚖️ Feedback Preserved

Unlike exogenous GH, tesamorelin preserves IGF-1–mediated negative feedback. This self-limiting control explains the more favorable glycemic profile vs. direct GH administration.

📊

PK note: Absorption is rapid (Tmax ~0.15 h). Half-life is short (~8-38 min depending on formulation), but the drug’s effect outlasts plasma levels by stimulating a GH pulse sequence that drives metabolic effects.

📊

Clinical Outcomes

📈 Phase 3 Trial Results

VAT reduction is the primary, most reproducible outcome. Across phase 3 trials, tesamorelin lowered VAT by ~15-20% at 26 weeks, maintained through 52 weeks when therapy continued, with no clinically significant loss of subcutaneous fat.

15-20% VAT Reduction At 26-52 weeks in HIV lipodystrophy ≥8% Responder Threshold Predicts ↓TG and ↑adiponectin Neutral Glycemic Effect No deterioration in 12-wk T2D trial ↓ Liver Fat Hepatic Benefit Slowed fibrosis progression

🎯 Responder Analysis

In pooled analysis, responders with ≥8% VAT loss showed lower triglycerides and higher adiponectin, without worsened glucose homeostasis.

“How much VAT you remove” predicts downstream metabolic benefit.

🫁 Liver Outcomes

In randomized trials, tesamorelin reduced liver fat and slowed fibrosis progression in people with HIV and fatty liver disease (NAFLD/MASLD).

Important given the overlap of VAT expansion and hepatic steatosis.

✅

Body image: Patient-reported belly profile and body-image distress improved in trials — a clinically meaningful outcome beyond the metabolic numbers.

⚠️ Safety Signals

• 💉 Common: Injection-site reactions, arthralgia, peripheral edema, myalgia
• 📈 IGF-1 rises predictably — monitor if exceeds reference ranges
• 🩸 Glucose: Transient early FG rise in some; NOT sustained; no deterioration in T2D
• 🧬 Antibodies: ~50% develop IgG but did NOT blunt VAT/IGF-1 response
• 🚫 Contraindications: Active malignancy, pregnancy, disrupted HPA axis

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Comparison

For visceral adiposity in HIV-associated lipodystrophy, tesamorelin is the only FDA-approved peptide with RCT evidence of VAT reduction and liver-fat benefits. Other peptides act on the GH axis but lack comparable VAT-targeted outcomes.

Tesamorelin

GHRH Receptor Agonist (44 AA) t½ ~8-38 min

FDA approved. GHRH(1-44) with DPP-IV resistance. Daily SC. ~15-20% VAT reduction. Neutral glycemic. Liver fat ↓.

FDA Approved VAT RCT Data Liver Benefits

Sermorelin

GHRH Receptor Agonist (29 AA) t½ ~8-12 min

GHRH(1-29). Daily SC. Shorter sequence. No VAT reduction RCTs in HIV. Limited metabolic data.

No VAT Data Limited Evidence

CJC-1295 (DAC)

Long-Acting GHRH Analogue t½ ~6-8 days

Albumin-binding via DAC. Weekly or less. Sustained IGF-1 rise. No VAT reduction RCTs in HIV.

Long-Acting No VAT Data

Ipamorelin

Ghrelin/GHSR Agonist (5 AA) t½ ~2 hours

Selective GH secretagogue without ACTH/cortisol rise. 1-3×/day. No VAT reduction RCTs. Different receptor target.

GHSR Target No VAT Data 💡

Why not just give GH? Exogenous GH can reduce insulin sensitivity acutely and at months. Tesamorelin’s GHRH-mediated physiology has shown neutral glycemic effects in T2D over 12 weeks — the preserved feedback is the key difference.

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FAQ

What is tesamorelin? A synthetic GHRH analogue that stimulates the pituitary to release GH in physiologic pulses, raising IGF-1 and driving selective visceral fat reduction in adults with HIV-associated lipodystrophy. It is the only peptide FDA-approved for this purpose. How much fat reduction can I expect? RCTs show ~15-20% VAT reduction after 26-52 weeks, with maintenance if treatment continues. Subcutaneous fat is largely preserved. Responders (≥8% VAT loss) also show better triglycerides and adiponectin. Does it worsen blood sugar? No deterioration of glycemic control was seen in a 12-week randomized trial in type 2 diabetes. In HIV cohorts, a transient early fasting glucose uptick has been observed but was NOT sustained. The label still advises glucose monitoring. How does it affect the liver? Tesamorelin reduces liver fat and slows fibrosis progression in people with HIV and fatty liver disease, linking VAT reduction to hepatic benefits in this population. Why not just use GH directly? Exogenous GH can reduce insulin sensitivity acutely and chronically. Tesamorelin preserves physiologic feedback — IGF-1 provides self-limiting control of GH output. This explains its more favorable glycemic profile. How should I store it? Lyophilized vials at room temp (20-25°C), protected from light. After reconstitution, use IMMEDIATELY — do NOT refrigerate or store. Tesamorelin gels at cold temperatures unlike most peptides. ✅

Bottom line: Tesamorelin is the only FDA-approved peptide for HIV-associated lipodystrophy with robust RCT evidence of ~15-20% VAT reduction, liver-fat benefits, and neutral glycemic profile. Its GHRH-mediated mechanism preserves physiologic feedback — the key advantage over direct GH. Store reconstituted solution at room temperature (unique for peptides) and use immediately.