Tesamorelin
Also known as TH9507, Egrifta, Egrifta SV, Egrifta WR, trans-3-hexenoyl-GHRH(1-44)
FDA-approved GHRH analogue that reduces visceral abdominal fat in HIV-associated lipodystrophy.
At a glance
- Category
- Growth hormone
- Status
- approved drug
- Route
- subcutaneous, in the abdomen with rotation of injection sites
- Half-life
- 26 minutes in healthy subjects and 38 minutes in HIV-infected patients after 14 days of subcutaneous administration of the original 1 mg-per-vial Egrifta formulation 5. The Egrifta SV formulation is not identical here: its label gives a mean elimination half-life of 8 minutes in healthy subjects after a single 1.4 mg dose 4
- Onset
- IGF-1 rises within 2 weeks; reduction of visceral fat measurable after approximately 3 months, maximum effect around 6 months
- Molecular weight
- 5135.9 g/mol (free base)
- Sequence
- trans-3-hexenoyl-GHRH(1-44)-NH2: the full human GHRH 1-44 with a trans-3-hexenoyl group on the N-terminal tyrosine
Approved by the FDA in 2010 (Egrifta) for the reduction of excess abdominal fat in adults with HIV-associated lipodystrophy 5; since succeeded by the Egrifta SV and Egrifta WR formulations, which carry the same indication 4. Not registered in the European Union: the marketing authorisation application was withdrawn by the applicant on 21 June 2012, after the CHMP took the view that the data did not allow it to conclude on a positive benefit-risk balance 6.
Doping status: Prohibited at all times (WADA S2, GH-releasing factors)
Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.
Mechanism of action
Tesamorelin is a synthetic analogue of the full human growth hormone-releasing hormone (GHRH 1-44), to which a trans-3-hexenoyl group has been attached at the N-terminus. This fatty acid group protects the molecule against breakdown by dipeptidyl peptidase-4 and extends the half-life from a few minutes (natural GHRH) to approximately half an hour.
It binds the GHRH receptor on the somatotroph cells of the anterior pituitary and stimulates the synthesis and pulsatile release of growth hormone via the cAMP/PKA pathway. It is therefore a GHRH analogue and not a ghrelin receptor agonist: it acts through a different receptor from ipamorelin, hexarelin, GHRP-2, GHRP-6 and MK-677. Those two classes reinforce each other, which is the basis for combination protocols — with tesamorelin, however, that does not happen in registered use.
The favourable effect on visceral fat runs via the raised GH and IGF-1. Growth hormone promotes lipolysis specifically in visceral adipose tissue, which has a high density of GH receptors, and inhibits the conversion of cortisone to cortisol in adipose tissue. Importantly, the effect is selective for visceral fat: subcutaneous fat remained largely unchanged in the registration studies 2, which fits the clinical problem in HIV lipodystrophy.
Because the negative feedback via IGF-1 and somatostatin remains intact, GH release stays pulsatile and within physiological limits — unlike with exogenous growth hormone. The effect disappears almost entirely after stopping: in the extension phase of the phase 3 studies, visceral fat in patients switched to placebo returned to baseline. Tesamorelin is therefore a maintenance treatment, not a one-off intervention.
What the research shows
Tesamorelin is the best-substantiated agent in this category. Two large randomised, double-blind, placebo-controlled phase 3 studies with more than 800 participants in total showed a reduction in visceral adipose tissue of approximately 15-18 per cent after 26 weeks, which led to registration. The evidence, however, applies exclusively to the HIV lipodystrophy population; there is no registration evidence for use in healthy adults for body composition or ageing.
Research in humans
Falutz et al. (NEJM 2007) showed a significant reduction in visceral adipose tissue at 2 mg tesamorelin per day versus placebo in a phase 3 study 1. A pooled analysis of both phase 3 studies with safety extension (Falutz et al., JCEM 2010, n=806) confirmed the reduction in visceral fat, improvements in triglycerides and the total cholesterol/HDL ratio, and showed that the effect disappeared after stopping 2. Later research has studied tesamorelin in non-alcoholic fatty liver disease in HIV, with reduction of liver fat as the outcome.
Animal and lab research
Preclinical research confirms the extended stability relative to natural GHRH and the dose-dependent GH release. Given the size of the human evidence base, the animal data are of limited importance.
Caveats. The study population was specific: HIV-infected adults with an increased waist circumference, largely men, on antiretroviral therapy. Generalisation to healthy adults is not substantiated. The studies ran 26 weeks plus extension; long-term safety over years, including oncological risk, has not been established. The research was funded by the manufacturer (Theratechnologies). The effect disappears after stopping, which means continuous treatment and therefore continuous exposure. Cost and availability are a practical obstacle in Europe, since there is no EU registration.
What it is used for
- Registered: reduction of excess abdominal fat in HIV-infected adults with lipodystrophy 4
- Studied: non-alcoholic fatty liver disease (NAFLD/NASH) in people with HIV
- Off-label: raising GH and IGF-1 and reducing visceral fat in people without HIV — not supported by registration research and not approved
- Studied in smaller trials on cognition in older adults with mild cognitive impairment
Dosing
- The dose of 1.4 mg 4 and 2 mg 5 respectively comes directly from the FDA-approved product information and is the only validated dose in this whole category of agents.
- The two formulations differ in dose, number of vials required, reconstitution instructions and storage conditions — they are not interchangeable 4.
- IGF-1 must be monitored regularly in all patients, and discontinuation should be considered in patients with persistent elevations 5.
- Glucose status should be evaluated before starting and monitored periodically during treatment: in the phase 3 trials 4.5 per cent of tesamorelin patients versus 1.3 per cent on placebo reached an HbA1c of 6.5 per cent or above by week 26 5.
- Doses circulating off-label for non-HIV use (often 1-2 mg per day or every other day) come from user protocols and are not substantiated in controlled research.
These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.
Protocols
Egrifta SV / Egrifta WR (2 mg per vial) for HIV-associated lipodystrophy
approved product informationSource: FDA prescribing information, EGRIFTA SV, 2019
| Once daily | 1.4 mg (0.35 ml of the reconstituted solution) subcutaneously into the abdomen, rotating the injection site |
|---|
This dose applies only to the 2 mg per vial formulation. The 1 mg per vial formulation is dosed differently, and the label states that the two differ in dose, number of vials per dose, reconstitution and storage. They are not interchangeable.
Egrifta original 1 mg-per-vial formulation, HIV-associated lipodystrophy
approved product informationSource: FDA prescribing information, EGRIFTA, 2010
| Once daily | 2 mg subcutaneously (each vial of this formulation contains 1 mg of tesamorelin) |
|---|
The higher milligram figure is not a higher exposure: the two formulations were shown to give comparable systemic exposure. Reading '2 mg' off this label and drawing it from an Egrifta SV vial would deliver more than the intended dose.
Off-label fat-loss use (user-reported)
user protocol — not validatedSource: The pattern repeated across bodybuilding and anti-ageing forums together with research-chemical vendor labelling of tesamorelin powder
This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.
| Most commonly reported daily amount | 1-2 mg subcutaneously, often taken at night, sometimes split |
|---|---|
| Reported alternative schedule | every other day, or five days on and two off, to stretch supply |
| Reported stacking | frequently combined with a ghrelin-receptor agonist such as ipamorelin — a pairing the registered indication never uses |
The label directs 1.4 mg (or 2 mg of the older formulation) once daily for excess abdominal fat in HIV-associated lipodystrophy, reconstituted from the registered kit with the supplied sterile water and injected immediately. Users self-reconstitute grey-market powder for visceral fat loss and 'GH optimisation' in people without HIV — an off-label purpose with no controlled support — and diverge from the schedule freely: nightly, every other day, or five-on-two-off, and commonly stacked with a GHRP, which registered use does not do. Reported daily amounts cluster at 1-2 mg but the frequency does not converge, and none of it rests on a trial in this population. The predictable problems carry over from the label: injection-site reactions, fluid retention and carpal-tunnel-type symptoms, and a real glucose signal — 4.5% of trial patients reached an HbA1c of 6.5% or more by week 26 — which nobody self-dosing is monitoring, alongside an IGF-1 rise of unknown long-term consequence.
Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.
Reconstitution
- Vial sizes
- 1 mg (Egrifta, original formulation), 2 mg (Egrifta SV and Egrifta WR)
- Solvent
- sterile water for injection, supplied in the package — the registered product does not use bacteriostatic water
- Storage
- Egrifta SV: powder at room temperature (20-25 °C). Original Egrifta: store refrigerated (2-8 °C). After reconstitution, administer immediately in both cases; do not store.
Worked example
Egrifta SV: one 2 mg vial is dissolved in 0.5 ml sterile water; of this, 0.35 ml (= 1.4 mg) is administered subcutaneously. With the original Egrifta, two 1 mg vials were each dissolved in 1 ml and combined into a 2 mg dose.
Follow only the package leaflet of the relevant formulation — reconstitution instructions and storage conditions differ substantially between Egrifta, Egrifta SV and Egrifta WR. Swirl gently until the powder has dissolved; do not shake. With the registered product the reconstituted solution is not kept for later use.
Work it out for Tesamorelin
Safety
Side effects
- Injection site reactions: erythema, pruritus, pain, urticaria, haemorrhage — injection site erythema and pruritus are among the reactions reported in more than 5 per cent of patients, and injection site reactions occurred in 17 per cent on tesamorelin versus 6 per cent on placebo 4
- Joint pain (arthralgia) — reported in more than 5 per cent of patients 4
- Peripheral oedema and fluid retention, thought to be related to the induction of GH secretion; transient or resolving on discontinuation 4
- Tingling and numbness in the hands; carpal tunnel syndrome is named in the product information as a manifestation of fluid retention 4
- Glucose intolerance and new-onset diabetes: in the phase 3 trials 4.5 per cent of tesamorelin patients versus 1.3 per cent on placebo had an HbA1c of 6.5 per cent or above at week 26, an intent-to-treat hazard odds ratio of 3.3 (CI 1.4-9.6) for developing diabetes relative to placebo 5
- Myalgia and pain in extremity 4
- Rash and urticaria 5
- Nausea, vomiting
- Hypersensitivity reactions — these occurred in 3.6 per cent of patients in the phase 3 trials and included pruritus, erythema, flushing, urticaria and other rash; hypersensitivity to tesamorelin or to the excipient mannitol is a contraindication 5
- Elevation of IGF-1, whose long-term consequences are unknown; the label directs monitoring IGF-1 and considering discontinuation with persistent elevations (for example above 3 SDS) 4
Do not use if
- Active malignancy, whether newly diagnosed or recurrent — an absolute contraindication in the FDA-approved product information. Any preexisting malignancy should be inactive and its treatment complete before starting therapy 45.
- Disruption of the hypothalamic-pituitary axis through hypophysectomy, hypopituitarism, pituitary tumour or surgery, head irradiation or head trauma 45
- Pregnancy — modifying visceral adipose tissue offers no benefit in a pregnant woman and could result in fetal harm 4
- Known hypersensitivity to tesamorelin or to the excipients, mannitol among them 45
- Caution in diabetes mellitus or impaired glucose tolerance: glucose status should be evaluated before starting and monitored during therapy, and discontinuation considered in patients who develop glucose intolerance without a clear efficacy response 4
- Caution in existing retinopathy — patients with diabetes should be monitored at regular intervals for development or worsening of retinopathy 4
- Acute critical illness — the label advises considering discontinuation in critically ill patients, citing increased mortality 4
- Caution in severe renal or hepatic impairment — pharmacokinetics in renal or hepatic impairment have not been studied 4
Interactions
Co-administration with simvastatin, a sensitive CYP3A substrate, showed no significant impact on simvastatin pharmacokinetics, suggesting tesamorelin does not significantly affect CYP3A activity; other CYP450 isoenzymes have not been evaluated 5. The label nonetheless notes that GH may alter the clearance of compounds metabolised by CYP450 liver enzymes — corticosteroids, sex steroids, anticonvulsants and ciclosporin are named — and advises careful monitoring when tesamorelin is combined with such drugs 5. Growth hormone inhibits 11-beta-hydroxysteroid dehydrogenase type 1, the enzyme converting cortisone to cortisol, so patients on glucocorticoid replacement may need their maintenance or stress doses adjusted 5. Raised GH and IGF-1 reduce insulin sensitivity, so the requirement for insulin or oral antidiabetics may increase. Glucocorticoids and somatostatin analogues blunt the GH response.
Common questions
What is tesamorelin (Egrifta) used for?
Does tesamorelin cause general weight loss or build muscle?
What is the difference between tesamorelin, sermorelin and CJC-1295?
Is tesamorelin banned in sport?
Sources
- Metabolic effects of a growth hormone-releasing factor in patients with HIVNew England Journal of Medicine, 2007
- Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in HIV-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension dataJournal of Clinical Endocrinology & Metabolism, 2010
- Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extensionJournal of Acquired Immune Deficiency Syndromes, 2010
- EGRIFTA SV (tesamorelin) for injection — FDA prescribing informationUS Food and Drug Administration, 2019
- EGRIFTA (tesamorelin for injection) — original FDA prescribing informationUS Food and Drug Administration, 2010
- Egrifta: withdrawal of the marketing authorisation applicationEuropean Medicines Agency, 2012