Tesamorelin
Tesamorelin is a synthetic growth hormone-releasing hormone (GHRH) analogue approved under the brand name Egrifta for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy.
Tesamorelin is a synthetic analogue of the full 44-amino acid growth hormone-releasing hormone (GHRH), modified with a trans-3-hexenoic acid group at the N-terminus to enhance stability and potency. It is FDA-approved under the brand name Egrifta for the reduction of excess visceral abdominal fat in HIV-infected patients with lipodystrophy, and is actively researched for applications in liver fat reduction, cognitive function, and cardiovascular health.
Overview
Tesamorelin was developed by Theratechnologies as a stabilized form of human GHRH(1-44). The addition of trans-3-hexenoic acid to the N-terminus protects the peptide from enzymatic degradation by dipeptidyl peptidase IV (DPP-IV), extending its biological activity compared to native GHRH. It received FDA approval in 2010 specifically for the treatment of HIV-associated lipodystrophy, a condition characterized by abnormal accumulation of visceral adipose tissue (VAT) that increases cardiometabolic risk. Tesamorelin stimulates pulsatile growth hormone release through the physiological GHRH receptor pathway, elevating IGF-1 levels and promoting lipolysis of visceral fat stores.
Mechanism of Action
Tesamorelin binds to GHRH receptors on somatotroph cells in the anterior pituitary gland, stimulating the synthesis and pulsatile secretion of endogenous growth hormone. The trans-3-hexenoic acid modification at the N-terminus confers resistance to DPP-IV cleavage, which is the primary route of inactivation for native GHRH, resulting in improved pharmacokinetic properties.
The resulting increase in circulating GH promotes lipolysis, particularly in visceral adipose depots, while also elevating IGF-1 levels. Because tesamorelin works through the physiological GHRH axis, GH release remains subject to somatostatin-mediated negative feedback, reducing the risk of supraphysiological GH concentrations compared to direct GH administration. This pulsatile, feedback-regulated mechanism is believed to contribute to preferential visceral fat reduction without significant loss of subcutaneous adipose tissue.
Reconstitution Calculator
Tesamorelin
Tesamorelin is a synthetic analogue of the full 44-amino acid growth hormone-rel
Exceeds syringe capacity
Dose requires 1.400mL but syringe holds 1mL. Increase BAC water, use a larger syringe, or split injections.
Set up a clean workspace with all supplies ready.
7x / week for weeks
Research
Cognitive Function
A randomized controlled trial in older adults demonstrated that tesamorelin improved executive function and verbal memory compared to placebo, with effects correlated to increases in IGF-1 levels. These findings suggest a potential role for GHRH axis stimulation in age-related cognitive decline. Baker et al. (2012) — Arch. Neurol.
Visceral Adipose Tissue and Body Composition
Tesamorelin consistently reduces visceral adipose tissue by 15-20% in clinical trials, with concurrent improvements in triglyceride levels and waist circumference. The reduction is selective for visceral fat, with minimal impact on subcutaneous adipose tissue or lean body mass, distinguishing it from caloric restriction approaches.
IGF-1 Elevation
Tesamorelin reliably elevates IGF-1 levels into the upper-normal physiological range, reflecting increased endogenous GH secretion. This elevation mediates many of the downstream metabolic effects, including improved body composition and potential neuroprotective benefits.
HIV-Associated Lipodystrophy
The pivotal Phase 3 trial demonstrated that tesamorelin significantly reduced visceral adipose tissue in HIV-infected patients with abdominal fat accumulation. Patients receiving tesamorelin showed an approximately 15% reduction in trunk fat compared to placebo over 26 weeks, with improvements in patient-reported body image distress and lipid profiles. Falutz et al. (2007) — JAMA
Sustained efficacy was confirmed in an extension study, demonstrating that continued treatment maintained VAT reductions over 52 weeks, while discontinuation led to visceral fat re-accumulation. Falutz et al. (2010) — JAIDS
Hepatic Fat and NASH
Research has explored tesamorelin's effects on hepatic steatosis. A randomized controlled trial demonstrated that tesamorelin significantly reduced liver fat content in HIV-infected patients with nonalcoholic fatty liver disease, suggesting potential applications beyond lipodystrophy. Stanley et al. (2014) — JCEM
Ongoing & Future Research
Several active and recently completed clinical trials continue to explore tesamorelin's therapeutic potential beyond HIV lipodystrophy:
-
NCT02196831: A randomized, double-blind, placebo-controlled trial investigating tesamorelin for the treatment of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in HIV-infected individuals. This study builds on earlier findings showing hepatic fat reduction and evaluates effects on liver fibrosis biomarkers and histological endpoints. ClinicalTrials.gov: NCT02196831
-
NCT03091374: A Phase 2 randomized controlled trial examining the effects of tesamorelin on cognitive function in older adults at risk for Alzheimer's disease. This study extends Baker et al.'s earlier findings by evaluating tesamorelin's effects on brain amyloid burden (via PET imaging), cerebrospinal fluid biomarkers, and detailed neuropsychological testing over 12 months. ClinicalTrials.gov: NCT03091374
-
NCT04064177: A study evaluating the effects of tesamorelin on liver fibrosis markers and hepatic steatosis in people living with HIV who have evidence of NAFLD. This trial focuses specifically on fibrosis endpoints and uses transient elastography (FibroScan) and MRI-PDFF to quantify treatment response. ClinicalTrials.gov: NCT04064177
Future research directions include investigation of tesamorelin in non-HIV populations with metabolic syndrome and NAFLD, combination protocols with GLP-1 receptor agonists for synergistic metabolic benefits, and longer-term studies evaluating cardiovascular outcomes.
Comparison to Related Compounds
| Feature | Tesamorelin | Sermorelin | CJC-1295 DAC | Direct GH (Somatropin) | Ibutamoren (MK-677) |
|---|---|---|---|---|---|
| Structure | Modified GHRH(1-44) + trans-3-hexenoic acid | Truncated GHRH(1-29)NH2 | Modified GRF(1-29) + Drug Affinity Complex | Recombinant 191-AA protein | Non-peptide GHS-R agonist |
| Half-life | 26-38 min | 10-20 min | ~6-8 days | 2-3 hours | ~24 hours (oral) |
| Administration | Daily SC injection | Daily SC injection | Weekly SC injection | Daily SC injection | Oral, daily |
| GH Release Pattern | Pulsatile, feedback-regulated | Pulsatile, feedback-regulated | Sustained elevation, blunted pulsatility | Direct supraphysiological | Pulsatile via ghrelin receptor |
| FDA Status | Approved (Egrifta) | Previously approved (now discontinued) | Research only | Approved (multiple indications) | Research only |
| IGF-1 Elevation | Yes, moderate | Yes, mild-moderate | Yes, sustained | Yes, significant | Yes, sustained |
| DPP-IV Resistance | Yes (trans-3-hexenoic acid) | No (rapidly degraded) | Yes (DAC technology) | N/A | N/A |
Tesamorelin vs Sermorelin: Sermorelin is a truncated GHRH(1-29)NH2 that retains full receptor binding activity but is rapidly degraded by DPP-IV, resulting in a half-life of only 10-20 minutes and lower peak GH responses. Tesamorelin's trans-3-hexenoic acid modification confers DPP-IV resistance, producing more robust and reproducible GH pulses. Tesamorelin also retains the full 44-amino acid GHRH sequence, which may contribute to enhanced receptor affinity and biological potency Sackmann-Sala et al. (2009) — PMID: 19275468.
Tesamorelin vs CJC-1295 DAC: CJC-1295 DAC uses a Drug Affinity Complex to bind serum albumin, extending half-life to approximately 6-8 days. However, this prolonged exposure produces sustained GH elevation that blunts normal pulsatility and may desensitize GHRH receptors over time. Tesamorelin's short half-life preserves physiological pulsatile GH release and somatostatin-mediated feedback Teichman et al. (2006) — PMID: 16352683.
Tesamorelin vs Direct GH Administration: Exogenous GH bypasses pituitary regulation entirely, producing supraphysiological GH levels that can cause insulin resistance, fluid retention, carpal tunnel syndrome, and increased cancer risk. Tesamorelin stimulates endogenous GH release through the physiological axis, maintaining feedback regulation and producing more moderate, physiological GH elevations Falutz et al. (2007) — PMID: 17519413.
Safety Profile
Tesamorelin has a well-characterized safety profile from extensive clinical trials and post-marketing surveillance. Common side effects include injection site reactions (erythema, pruritus, pain), arthralgia, peripheral edema, and myalgia. IGF-1 levels should be monitored during treatment, as sustained elevations above the age-adjusted normal range may necessitate dose adjustment or discontinuation.
Tesamorelin is contraindicated in patients with active malignancy, as GH axis stimulation could theoretically promote tumor growth. It is also contraindicated during pregnancy due to potential effects on fetal development. Patients should be monitored for changes in glucose metabolism, as GH elevation can impair insulin sensitivity. Clinical trials have shown modest increases in fasting glucose and HbA1c in some patients, though frank diabetes is uncommon. Hypersensitivity reactions to tesamorelin or mannitol (an excipient) have been reported rarely.
Pharmacokinetic Profile
Tesamorelin — Pharmacokinetic Curve
Subcutaneous injection (daily)Quick Start
- Typical Dose
- 1.4-2mg daily (FDA-approved: 2mg for HIV lipodystrophy)
- Frequency
- Once daily (evening preferred for GH rhythm)
- Route
- Subcutaneous injection (daily)
- Cycle Length
- Continuous therapy for maintained benefits
- Storage
- Powder: 20-25°C. Egrifta SV: use immediately. Egrifta WR: room temp up to 7 days
Molecular Structure
- Formula
- C221H366N72O67S
- Weight
- 5 Da
- Length
- 44 amino acids
- CAS
- 218949-48-5
- PubChem CID
- 16136245
- Exact Mass
- 1630.7488 Da
- LogP
- 3.5
- TPSA
- 513 Ų
- H-Bond Donors
- 17
- H-Bond Acceptors
- 18
- Rotatable Bonds
- 41
- Complexity
- 3390
Identifiers (SMILES, InChI)
InChI=1S/C82H103ClN18O16/c1-45(2)35-60(72(107)92-59(16-9-10-33-87-46(3)4)80(115)101-34-12-17-68(101)79(114)88-47(5)70(84)105)93-74(109)63(38-51-23-30-58(31-24-51)91-81(85)116)95-76(111)64(39-50-21-28-57(29-22-50)90-71(106)66-42-69(104)100-82(117)99-66)97-78(113)67(44-102)98-77(112)65(41-53-13-11-32-86-43-53)96-75(110)62(37-49-19-26-56(83)27-20-49)94-73(108)61(89-48(6)103)40-52-18-25-54-14-7-8-15-55(54)36-52/h7-8,11,13-15,18-32,36,43,45-47,59-68,87,102H,9-10,12,16-17,33-35,37-42,44H2,1-6H3,(H2,84,105)(H,88,114)(H,89,103)(H,90,106)(H,92,107)(H,93,109)(H,94,108)(H,95,111)(H,96,110)(H,97,113)(H,98,112)(H3,85,91,116)(H2,99,100,104,117)/t47-,59+,60+,61-,62-,63-,64+,65-,66+,67+,68+/m1/s1
MEUCPCLKGZSHTA-XYAYPHGZSA-NResearch Indications
Weight Loss
FDA-approved indication showing 15-20% visceral fat reduction in clinical trials.
Unique mechanism that reduces dangerous visceral fat while sparing subcutaneous fat.
Maintained weight loss with continuous treatment over 52+ weeks in clinical studies.
Metabolic
12.3% reduction in triglyceride levels.
7.2% improvement in cholesterol markers.
37% liver fat reduction over 12 months.
Body Composition
Preserves lean muscle mass during fat loss.
26% increase in IGF-1 levels.
Research Protocols
subcutaneous Injection
FDA-approved GHRH analog (Egrifta). Administered subcutaneously, preferably in the evening.
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| Titration | 1,000 mcg (1 mg) | Once daily | Week 1(Evening administration preferred) |
| Full dose | 2,000 mcg (2 mg) | Once daily | Weeks 2-12+(Standard cycle: 12-26 weeks. Clinical trials support up to 52 weeks.) |
Reconstitution Guide (5mg vial + 2.5mL BAC water)
- Wipe vial tops with alcohol swab
- Draw 2.5 mL bacteriostatic water into syringe
- Inject slowly down the inside wall of the peptide vial
- Gently swirl to dissolve — never shake
- Resulting concentration: 2.0 mg/mL
- For 1 mg dose: draw 50 units (0.50 mL)
- For 2 mg dose: draw 100 units (1.00 mL)
- Store reconstituted vial refrigerated at 2-8°C
Interactions
Peptide Interactions
IGF-1 levels should be monitored during treatment, as sustained elevations above the age-adjusted normal range may necessitate dose adjustment or discontinuation.
What to Expect
What to Expect
IGF-1 levels begin to rise, possible mild water retention or joint discomfort
Early metabolic changes; improved energy/sleep
Visible visceral fat reduction begins, waist circumference may decrease
Peak effects achieved with significant body composition improvements
Safety Profile
Common Side Effects
- Injection site reactions (17%)
- Joint pain (13%)
- Water retention
Contraindications
- Active malignancy
- Pituitary disorders
- Pregnancy
Discontinue If
- Development of diabetes or severe glucose intolerance (HbA1c ≥6.5%)
- Signs of malignancy
- Severe hypersensitivity reactions
- Excessive IGF-1 elevation (>2 SD above normal) with acromegaly symptoms
Quality Indicators
What to look for
- FDA-approved formulations (Egrifta SV/WR from licensed pharmacy)
- White crystalline powder (uniform, cake-like)
- Clear reconstituted solution (colorless, no particles)
- Proper packaging (sealed vials, intact stoppers)
Caution
- Compounded formulations may have quality/potency variability
Red flags
- Discolored or cloudy solution (yellow/brown indicates degradation)
- Visible particles or precipitate
Frequently Asked Questions
References (9)
- [1]LIPO-010 FDA Pivotal Trial (2010)
- [2]CTR-1011 Extended Safety Study (2011)
- [3]NAFLD Treatment Trial (2019)
- [4]Cognitive Enhancement Study (2012)
- [9]Stanley TL et al — Tesamorelin reduces cardiovascular biomarkers and hepatic fat in HIV-associated NAFLD (2023)
- [5]Falutz, J. et al Metabolic effects of a growth hormone-releasing factor in patients with HIV JAMA (2007)
- [6]
- [7]Stanley, T. L. et al Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation JCEM (2014)
- [8]Baker, L. D. et al Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults Arch. Neurol. (2012)
TB-500
TB-500 is a synthetic fragment of thymosin beta-4, a 43-amino acid protein involved in actin regulation, tissue repair, wound healing, and anti-inflammatory signaling across multiple organ systems.
Testagen
Testagen is a complex peptide bioregulator preparation targeting testicular tissue, developed at the St. Petersburg Institute of Bioregulation and Gerontology for research in male reproductive aging, testosterone regulation, and spermatogenesis. It is part of the Cytomed line of tissue-specific peptide bioregulators.