Tesamorelin
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FDA-approved GHRH analog (Egrifta); 44-amino acid modified growth hormone-releasing hormone with trans-3-hexenoic acid modification for DPP-IV resistance. Approved for HIV-associated lipodystrophy (2010).
Quick Facts
| Property | Value |
|---|---|
| Also Known As | Egrifta, Egrifta SV, TH9507, (trans-3-hexenoic acid)-GRF(1-44)-NH2 |
| Category | GH Axis / Metabolic |
| Sequence | 44-amino acid GHRH analogue (full-length + trans-3-hexenoic acid N-terminal modification) |
| Molecular Weight | ~5135 Da |
| Molecular Formula | C221H366N72O67S1 |
| PubChem CID | 44147413 |
| Administration | SubQ |
| Typical Dose Range | 1.4 mg (Egrifta SV) to 2 mg (Egrifta WR) daily |
| Half-Life | 26-38 minutes (terminal) |
| Storage | Lyophilized 2-8C (do NOT freeze); reconstituted use same day |
| FDA Status | FDA-Approved (Egrifta, HIV-associated lipodystrophy, November 2010) |
| WADA Status | Prohibited (S2 — Peptide Hormones, Growth Factors) |
Mechanism of Action
Tesamorelin is the only FDA-approved growth hormone-releasing hormone (GHRH) analog. It is a full-length 44-amino acid synthetic GHRH with a trans-3-hexenoic acid modification at the N-terminus that protects it from dipeptidyl peptidase-IV (DPP-IV) degradation, extending its biological activity relative to native GHRH(1-44). PMID 22298602
Unlike exogenous GH administration, tesamorelin stimulates endogenous GH (GH1, UniProt P01241) secretion from pituitary somatotrophs via GHRH receptor activation while preserving the physiological pulsatile secretion pattern. This results in a more favorable side effect profile compared to direct GH replacement, with lower risk of supraphysiological IGF-1 levels. The downstream GH/IGF-1 axis activation drives preferential lipolysis in visceral adipose tissue (VAT) through mechanisms that are incompletely characterized but likely involve differential beta-adrenergic receptor density and hormone-sensitive lipase activity in visceral vs. subcutaneous fat depots. PMID 31644039
A meta-analysis of body composition outcomes confirmed tesamorelin significantly reduces trunk fat and visceral adipose tissue while preserving or increasing lean mass, with effects sustained over 26-52 week treatment periods. PMID 41545261
Tesamorelin also reduces hepatic fat content via GH-mediated improvements in hepatic insulin sensitivity and lipid metabolism, providing a potential therapeutic avenue for NAFLD/MASLD. RCT data demonstrated significant reductions in liver fat fraction and improvements in hepatic fibrosis markers. PMID 25038357
An intriguing secondary finding from RCT data is cognitive improvement: tesamorelin improved executive function and verbal memory in both MCI patients and healthy older adults, likely through IGF-1-mediated neuroprotection and cerebrovascular effects. PMID 22869065
Key Research Areas
- HIV-Associated Lipodystrophy (FDA-approved): Significant VAT reduction (15-18%) sustained over 52 weeks in pivotal trials. PMID 22050344
- NAFLD/MASLD: RCT data showing liver fat reduction and hepatic transcriptomic improvements. PMID 32701508, PMID 25038357
- Cognitive Function: Improved executive function and verbal memory in healthy aging and MCI. PMID 22869065
- Body Composition Meta-Analysis: Confirmed trunk fat/VAT reduction and lean mass preservation. PMID 41545261
- Integrase Inhibitor-Associated Weight Gain: Efficacy in people with HIV on modern ART regimens. PMID 38905488
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 2 | Visceral/liver fat RCT, cognitive function RCT |
| Human observational | 1 | HIV + integrase inhibitors |
| Animal in vivo | 0 | — |
| In vitro | 0 | — |
| Systematic reviews / Meta-analyses | 1 | Body composition meta-analysis (Level I) |
| Narrative reviews | 4 | Drug reviews, pharmacology |
Clinical Applications
- Fat Loss — Preferential visceral adipose tissue reduction
- NAFLD — Hepatic fat reduction, fibrosis marker improvement
- Cognitive Enhancement — IGF-1-mediated neuroprotection in aging
- Sarcopenia — Lean mass preservation via GH axis stimulation
- Weight Management — Body recomposition
Protocols Using This Peptide
Ageless Peps Products
- AP-Tesamorelin-Vial — Tesamorelin Vial, $62
- AP-Tesa-Ipam-Blend — Tesamorelin/Ipamorelin Blend, $119
Dosing Reference
Research Dosing Ranges (from literature)
| Route | Dose Range | Frequency | Duration | Source |
|---|---|---|---|---|
| SubQ | 1.4 mg (Egrifta SV) | Once daily | Ongoing; reassess 6 months | FDA label |
| SubQ | 2 mg (Egrifta WR) | Once daily | Ongoing | FDA label |
| SubQ | 1-2 mg | Once daily | 12-16 weeks on / 8 weeks off | Off-label protocols |
Cycling
FDA-approved use is continuous with periodic reassessment. Off-label functional medicine protocols typically use 12-16 weeks on / 8 weeks off with IGF-1 monitoring every 3 months. Rotate injection sites on the abdomen. Administer before bedtime in a fasted state for optimal GH pulse.
Contraindications & Safety
- Contraindications: Pregnancy (Category X — absolute; IGF-1 crosses placenta); active malignancy (GH/IGF-1 tumor promotion); pituitary tumor or cranial irradiation; hypopituitarism (requires pituitary reserve for response)
- Common side effects: Peripheral edema, arthralgia, myalgia, nausea, injection site reactions; glucose intolerance (monitor HbA1c)
- Drug interactions: May alter insulin sensitivity; monitor in diabetic patients on hypoglycemics. Glucocorticoids may reduce efficacy.
- Pregnancy/nursing: Absolutely contraindicated (Category X)
- Special populations: ~50% of patients develop anti-tesamorelin antibodies (ADAs) which do not always reduce efficacy; monitor IGF-1 response
Synergistic Combinations
- Ipamorelin + Tesamorelin — GHRH + GHRP combination for enhanced GH pulse amplitude (available as AP-Tesa-Ipam-Blend)
- CJC-1295 NO DAC + Tesamorelin — Alternative GHRH pairing; similar mechanism but shorter-acting
- AOD-9604 + Tesamorelin — Additional targeted lipolysis pathway
- MOTS-C + Tesamorelin — Metabolic synergy (mitochondrial + GH axis)
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| 38905488 | Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors | 2024 | Observational |
| 32701508 | Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD | 2020 | RCT sub-study |
| 31644039 | Tesamorelin (comprehensive drug review) | 2019 | Review |
| 22298602 | Tesamorelin: a growth hormone-releasing factor analogue for HIV lipodystrophy | 2012 | Review |
| 22050344 | Spotlight on tesamorelin in HIV-associated lipodystrophy | 2011 | Review |
| 25038357 | Tesamorelin Reduces Visceral and Liver Fat | 2014 | RCT (Level I) |
| 22869065 | Tesamorelin Cognitive Function in MCI and Healthy Older Adults | 2012 | RCT (Level I) |
| 41545261 | Tesamorelin Body Composition Meta-Analysis | 2025 | Meta-analysis (Level I) |
References
- PMID 38905488 — Integrase inhibitor efficacy
- PMID 32701508 — Hepatic transcriptomics
- PMID 31644039 — Drug review
- PMID 22298602 — GHRH analog review
- PMID 22050344 — HIV lipodystrophy spotlight
- PMID 25038357 — Visceral/liver fat RCT
- PMID 22869065 — Cognitive function RCT
- PMID 41545261 — Body composition meta-analysis
Related
#peptide #gh-axis #metabolic #subq