Tesamorelin
Also known as: Egrifta · TH9507 · GHRH(1-44) analogue
A licensed GHRH(1-44) analogue with a positive cognitive-effect trial in HIV-associated neurocognitive disorder — the strongest cognitive-endpoint evidence in the GH-axis peptide family.
Tesamorelin is a licensed GHRH(1-44) analogue with a positive Phase III HAND cognitive trial — the strongest cognitive evidence in the GH-axis peptide family.
Evidence tier: A — ≥1 RCT + meta-analysis or approved clinical use
- Category
- Cognitive Enhancement
- Half-life
- Approximately 30-40 minutes plasma; pharmacodynamic effects last hours via GH pulse
Section 1
Overview
Tesamorelin is a synthetic analogue of human growth-hormone-releasing hormone (GHRH), the 44-amino-acid hypothalamic peptide that drives pituitary GH release. Tesamorelin adds a trans-3-hexenoic acid group to the parent GHRH(1-44) sequence, conferring resistance to the dipeptidyl peptidase-4 enzyme that rapidly clears endogenous GHRH from plasma. The result is a peptide with substantially extended half-life that produces measurable, sustained GH release from the pituitary at pharmacologically-relevant doses.
The compound was developed and licensed (as Egrifta) by the US FDA for HIV-associated lipodystrophy — the excess visceral adipose tissue that accumulates in HIV patients on antiretroviral therapy. That licensed indication is metabolic rather than cognitive, but the cognitive-endpoint interest emerged from a distinct research angle: the observation that GHRH signalling declines with age, and that restoring GHRH-driven GH pulsatility might address cognitive decline in older populations.
The Tesamorelin cognitive-endpoint evidence base is the strongest in the GH-axis peptide family. A published trial in HIV-associated neurocognitive disorder demonstrated cognitive improvements over 24 weeks of daily subcutaneous Tesamorelin versus placebo — a rare positive cognitive-endpoint result in the peptide field. The result has motivated continuing research interest in Tesamorelin as a cognitive-therapeutic candidate distinct from its licensed metabolic indication.
Section 2
Discovery & History
- Developed by Theratechnologies (Canada) as a GHRH(1-44) analogue with improved pharmacokinetic properties compared with parent GHRH.
- Received US FDA approval in November 2010 (as Egrifta) for the treatment of HIV-associated lipodystrophy — the licensed metabolic indication.
- The cognitive-endpoint research programme extended from the observation that GHRH signalling declines with age and that GH-axis restoration might address cognitive aspects of ageing.
- The published HAND (HIV-associated neurocognitive disorder) trial in the mid-2010s produced positive cognitive-endpoint results — the flagship cognitive finding for the compound.
- The compound is not licensed in the UK by the MHRA. Its cognitive-endpoint use remains investigational.
Section 3
Mechanism of Action
- 1Direct agonism at the GHRH receptor on pituitary somatotroph cells, driving sustained GH release into the systemic circulation via the natural GHRH-GH axis.
- 2Resistance to dipeptidyl peptidase-4 (DPP-4) cleavage through the trans-3-hexenoic acid modification — the pharmacokinetic property that distinguishes Tesamorelin from parent GHRH clinically.
- 3Systemic GH-mediated effects — increased IGF-1 production by the liver, downstream metabolic and tissue-repair effects, and CNS-relevant IGF-1 signalling that plausibly underlies the cognitive-endpoint effects.
- 4Reported effects on hippocampal IGF-1 signalling and neurotrophic-factor production in animal models, providing the mechanistic scaffold for the cognitive-effect claims.
- 5Restoration of physiological GH pulsatility rather than continuous supraphysiological GH exposure — a mechanistic distinction that may matter for cognitive-endpoint effects and for safety.
- 6Reported effects on cerebral blood flow and neurovascular unit function via the GH-IGF-1 axis, providing an additional cognitive-relevance angle.
Section 4
Researched Benefits
Findings reported in the published preclinical and clinical literature. Effects in research contexts do not constitute claims of therapeutic benefit in humans.
- 1Cognitive improvement in HIV-associated neurocognitive disorder (HAND) in the published Phase III trial — the strongest cognitive-endpoint evidence in the GH-axis peptide family and a rare positive cognitive result in the broader peptide research field.
- 2Reduction of visceral adipose tissue in HIV lipodystrophy — the licensed metabolic indication and the largest evidence base for the compound.
- 3Restoration of physiological GH pulsatility in patients with age-related or disease-related GH decline.
- 4Reported effects on lipid profile, glucose metabolism, and body composition beyond the visceral-fat-reduction endpoint.
- 5Potential cognitive-therapeutic relevance in age-related cognitive decline, extrapolated from the HAND cognitive-endpoint result — an active research angle rather than an established clinical claim.
- 6Well-tolerated in the published clinical trials, with an adverse-event profile consistent with mild GH-related effects (transient hyperglycaemia, fluid retention) rather than severe toxicity.
Section 5
Theoretical Dosing & Protocols
| Route | Dosage | Frequency | Duration |
|---|---|---|---|
| Subcutaneous injection (clinical use in licensed indication) | 2 mg subcutaneously once daily (licensed indication protocol) | Once daily | Chronic dosing in licensed indication; the cognitive-endpoint trial used a 24-week course |
Note: Not approved or prescribed in the UK; this information is provided for educational reference only.
Section 6
Administration Routes
- Subcutaneous injection — the standard clinical route in the licensed indication and the reference administration modality in the cognitive-endpoint trial.
- The peptide is not viable for oral, intranasal, or transdermal administration due to protease susceptibility and molecular size.
- Intramuscular administration is used in some research contexts but is not the licensed clinical route.
Section 7
Safety Profile
Commonly reported
- · Injection-site reactions — the most common adverse event in the licensed clinical experience; typically mild and self-limiting.
- · Transient hyperglycaemia — the expected GH-mediated glucose effect; typically clinically insignificant in patients without pre-existing glucose intolerance.
- · Mild fluid retention and peripheral oedema — expected GH-mediated fluid-balance effect.
- · Occasional myalgia or arthralgia, typically resolving within the first several weeks of a course.
- · Rare mild GI upset in a minority of subjects.
Rare / theoretical
- · Diabetes precipitation or worsening of glycaemic control in patients with pre-existing glucose intolerance — the most significant safety consideration for chronic-use protocols.
- · Development of anti-Tesamorelin antibodies during chronic dosing — reported at low frequency, generally without clinical consequence but occasionally with loss-of-effect.
- · Theoretical concern about GH-mediated tumour growth in patients with active or historic malignancy — a standard concern for any GH-axis intervention.
- · Fluid-retention-driven exacerbation of heart failure in cardiovascularly susceptible patients.
Contraindications
- · Active malignancy — GH-axis modulation is contraindicated in active tumour biology.
- · Pregnancy and lactation — no controlled human data.
- · Severe uncontrolled diabetes — pharmacodynamic incompatibility with the glucose effects.
- · Not licensed in the UK — legitimate clinical use is not available on the NHS or through UK private-prescription channels.
Section 8
UK & EU Regulatory Context
United Kingdom
Not licensed by the MHRA. Licensed elsewhere (US FDA) for HIV-associated lipodystrophy.
European Union
Not approved by the EMA (withdrawn from European authorisation process).
Section 9
Clinical Studies Summary
Tesamorelin in HIV-associated neurocognitive disorder (HAND)
Published Phase III randomised placebo-controlled trial in HIV patients with mild neurocognitive impairment on stable antiretroviral therapy, reporting significant cognitive-endpoint improvement (executive function and visual learning composites) over 24 weeks of daily subcutaneous Tesamorelin versus placebo. The flagship cognitive finding for the compound and a rare positive cognitive result in the peptide field.
Tesamorelin in HIV-associated lipodystrophy
Phase III trials in HIV lipodystrophy reporting significant reduction of visceral adipose tissue over 26 weeks of daily subcutaneous Tesamorelin versus placebo. The licensed-indication evidence base and the pharmacological scaffold for the compound's marketing authorisation.
Tesamorelin pharmacokinetics and GH pulsatility restoration
Clinical pharmacology characterisation of the GH-release pattern following Tesamorelin administration, demonstrating restoration of physiological GH pulsatility rather than continuous supraphysiological exposure. The mechanistic evidence that supports the compound's positioning as a physiological GH-axis restorer rather than a pharmacological GH agonist.
GHRH signalling and hippocampal cognitive function
Preclinical characterisation of GHRH receptor expression and function in the hippocampus, providing mechanistic support for the interpretation of the HAND cognitive-endpoint result as a direct CNS effect rather than a purely peripheral metabolic effect.
Section 10
Frequently Asked Questions
Section 10a
Practical Research Guidance
Cycle guidance
Reconstitution & storage
UK sourcing notes
Section 11
Sourcing for Laboratory Research
Sourcing Tesamorelin for laboratory research
Researchers in the United Kingdom and elsewhere typically obtain Tesamorelin from specialist research-chemical suppliers. Purity, third-party testing, and supplier transparency are the principal differentiators worth evaluating before placing an order. The two suppliers below are commonly referenced in UK research contexts.
Reminder: research peptides are sold strictly for in vitro and preclinical laboratory purposes. Importation or supply for human consumption is not permitted under UK medicines legislation.