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)
⚡ 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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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
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HIV-associated lipodystrophy — visceral fat reduction
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FDA approved — only peptide for this use
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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.
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.
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.
🛡️ 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.
🎯 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
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Common: Injection-site reactions, arthralgia, peripheral edema, myalgia
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IGF-1 rises predictably — monitor if exceeds reference ranges
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Glucose: Transient early FG rise in some; NOT sustained; no deterioration in T2D
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Antibodies: ~50% develop IgG but did NOT blunt VAT/IGF-1 response
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Contraindications: Active malignancy, pregnancy, disrupted HPA axis
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
FDA approved. GHRH(1-44) with DPP-IV resistance. Daily SC. ~15-20% VAT reduction. Neutral glycemic. Liver fat ↓.
Sermorelin
GHRH(1-29). Daily SC. Shorter sequence. No VAT reduction RCTs in HIV. Limited metabolic data.
CJC-1295 (DAC)
Albumin-binding via DAC. Weekly or less. Sustained IGF-1 rise. No VAT reduction RCTs in HIV.
Ipamorelin
Selective GH secretagogue without ACTH/cortisol rise. 1-3×/day. No VAT reduction RCTs. Different receptor target.
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.
FAQ
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.