Tesamorelin: Full Specification, Mechanism, Dosing and Evidence

Growth-hormone-releasing hormone is the 44-amino-acid signal the hypothalamus sends to the pituitary to trigger a growth hormone pulse. Tesamorelin is that entire sequence with a trans-3-hexenoic acid group attached to one end. Native GHRH is cut apart in the bloodstream within minutes by the enzyme DPP-4; the cap protects the cleavage site so the peptide survives long enough after a subcutaneous injection to reach the pituitary.

That makes it a secretagogue — a compound that causes something else to be secreted. It contains no growth hormone. It delivers the instruction, and the pituitary decides how much to release.

Tesamorelin was developed by Theratechnologies under the code TH9507 and is the active ingredient in Egrifta, which the FDA approved in November 2010 for one narrow indication: reduction of excess abdominal fat in adults with HIV who have lipodystrophy, a fat-redistribution syndrome associated with antiretroviral therapy. Later formulations, Egrifta SV and Egrifta WR, were approved for the same indication. That history is why tesamorelin has something most compounded peptides do not — randomised, placebo-controlled human trials with published results.

The compounded tesamorelin on this page shares the active peptide with Egrifta. It is not Egrifta; the difference is set out in the FDA section below.

It is not growth hormone, and it cannot substitute for it in someone whose pituitary cannot respond — the approved product is contraindicated where the hypothalamic–pituitary axis is disrupted for exactly that reason. It is not a weight-loss drug: the approved label states it is not indicated for weight-loss management because its effect on scale weight is neutral. And it is not a general fat-loss agent. The trial evidence is about visceral fat, the fat around the organs, and every trial that measured subcutaneous fat reported no significant change.

Tesamorelin binds the same pituitary receptor as native GHRH and triggers a growth hormone pulse. Because the release is pulsatile and still subject to somatostatin, the pattern looks like an amplified version of normal physiology rather than a flat, sustained elevation — the central distinction from injected growth hormone, which bypasses the pituitary altogether.

Growth hormone released in the pulse acts on the liver to produce IGF-1, which carries most of the signal to tissue. In the 2007 New England Journal of Medicine trial IGF-1 rose by 81% over 26 weeks; in the 2012 Archives of Neurology trial in older adults it rose by 117% and stayed within the physiological range. The size of that rise is why IGF-1 monitoring is written into the approved product's label, and why it is the number your physician actually looks at.

Growth hormone is lipolytic — it signals fat cells to release stored triglyceride — and visceral fat carries a higher density of the relevant receptors than subcutaneous fat. That explains the pattern every tesamorelin trial has reported: a measurable reduction in visceral fat on CT with no significant change in subcutaneous fat. Because visceral fat and liver fat travel together metabolically, the same signalling is the proposed basis for the liver-fat findings below.

This is the evidence the approval rests on. The first phase 3 trial, in the New England Journal of Medicine in 2007, randomised 412 people with HIV and abdominal fat accumulation to daily tesamorelin 2 mg or placebo for 26 weeks. Visceral fat on CT fell 15.2% on treatment and rose 5.0% on placebo; triglycerides fell 50 mg/dL against a 9 mg/dL rise; glycaemic measures did not differ. A second trial of the same design followed in the Journal of Acquired Immune Deficiency Syndromes in 2010.

A pooled analysis of both in the Journal of Clinical Endocrinology and Metabolism in 2010 covered 806 randomised patients with a 26-week safety extension. At week 26 visceral fat fell 24 cm² versus a 2 cm² rise on placebo, a treatment effect of −15.4%, with no significant change in subcutaneous fat. Patients kept on tesamorelin for 52 weeks maintained the reduction, and visceral fat returned toward baseline in those switched to placebo — worth knowing before you start.

The 2014 JAMA trial randomised 50 people with HIV and abdominal fat accumulation to tesamorelin 2 mg or placebo for six months: a 34 cm² reduction in visceral fat versus an 8 cm² rise on placebo, plus a modest reduction in liver fat by magnetic resonance spectroscopy. The 2019 Lancet HIV trial enrolled 61 people with HIV and non-alcoholic fatty liver disease for 12 months; hepatic fat fraction fell by an absolute 4.1% more than placebo, a 37% relative reduction, and 35% of treated participants reached a fat fraction under 5% against 4% on placebo. Fasting glucose and HbA1c did not differ. It is not an approved indication.

One randomised trial has tested tesamorelin outside HIV, in the Journal of Clinical Endocrinology and Metabolism in 2012: 60 abdominally obese adults with reduced growth hormone secretion, tesamorelin 2 mg or placebo for 12 months. Visceral fat fell 16 cm² versus a 19 cm² rise on placebo, with improvements in triglycerides, C-reactive protein and carotid intima-media thickness, no change in subcutaneous fat, and no change in glucose measures. It is one trial of 60 people selected for low GH secretion — but it is the most direct evidence that the visceral-fat finding is a property of the drug rather than of HIV.

The Archives of Neurology trial in 2012 randomised 152 adults aged 55 to 87, 66 with mild cognitive impairment, to tesamorelin 1 mg or placebo at bedtime for 20 weeks. It reported a favourable effect on a cognitive composite, driven mainly by executive function, in both groups; body fat fell 7.4%. Adverse events were mild but more frequent on the drug (68% versus 36%). A single 20-week trial whose authors call for longer ones — an interesting signal, not an established use.

Tesamorelin has randomised, double-blind, placebo-controlled human trials, including two phase 3 trials that supported an FDA approval. Roughly 1,100 people have been randomised to tesamorelin or placebo in the published trials above. That is a materially stronger evidence base than any other growth-hormone secretagogue prescribed as a compounded peptide, and it is why tesamorelin is usually the one a physician reaches for when the goal is specifically visceral fat.

What the trials share also limits them: every one used a fixed daily dose of 1 mg or 2 mg, most were in people with HIV, and the longest ran 12 months. None used the weekday-night schedule or the 0.5 mg dose on this page.

• It does not establish an effect on scale weight. The approved label calls the drug weight-neutral; the trials measured visceral fat on CT, not kilograms.
• It does not establish an effect on subcutaneous fat. Every trial that measured it reported no significant change.
• It does not establish results at the compounded dose or schedule. The human data is at 1–2 mg daily; 0.5 mg five nights a week is a physician's extrapolation.
• It does not establish long-term cardiovascular outcomes. The approved label says so explicitly.
• It does not establish that benefits persist after stopping. The extension data showed visceral fat returning toward baseline on placebo.
• It does not establish any effect in healthy adults with normal GH secretion who are not overweight, because no trial has enrolled them.

What people describe first is sleep — often deeper, sometimes with more vivid dreams — which fits a bedtime dose amplifying the slow-wave-sleep pulse. Some early fluid retention, joint stiffness or hand tingling can appear; the trials recorded these as the commonest non-injection-site effects and they generally settle or respond to a lower dose. Nobody should expect a visible change in the abdomen in two weeks.

IGF-1 has risen and settled, and this is the window in which prescribers describe recovery between training sessions and the first body-composition changes, where diet and training are in place. The follow-up IGF-1 and fasting glucose draw usually falls here, and it decides whether the dose stays where it is.

The trials measured their primary endpoint at six months. If visceral fat is the goal, this is the horizon on which to judge it — by waist measurement or imaging rather than the scale, which the evidence says will not move much. The approved label advises weighing the case for continuing in anyone who has not had a reduction in visceral fat by then, and that is a reasonable conversation to have with your physician.

No withdrawal is described. What the extension data does describe is visceral fat drifting back toward baseline over the six months after switching to placebo — the pattern of most metabolic therapies, where the effect is maintained while the signal is present.

The directions are written in millilitres and insulin-syringe units because that is what you can read off the barrel. 0.25 mL is 25 units on a U-100 syringe. You are not calculating anything — the number is printed on your medication. The milligram figure is there so you and your physician can relate the dose to the IGF-1 result.

Subcutaneous means into the fat layer, not the muscle. The abdomen is the usual site, rotated so the same spot is not used repeatedly. The dose is taken shortly before sleep so the pulse it triggers lands on top of the one slow-wave sleep already produces. The weekday-only schedule is a prescriber convention that gives the axis two nights without a signal each week; it is not trial-derived, and your physician may direct otherwise.

20 doses at five nights a week is exactly four weeks, which is why refills run on a 28-day cycle. One vial per fill, always — not a stockpile.

Refrigerated, and it ships that way in insulated packaging with ice packs. Beyond-use dating runs from first puncture and is printed on the label. Do not shake the vial.

Both are GHRH analogues acting on the same pituitary receptor. Sermorelin is the first 29 amino acids of GHRH and is cleared quickly; tesamorelin is the full 44-residue sequence with a stabilising cap and a longer action. The practical difference is the evidence: sermorelin's human data is older and smaller, tesamorelin's includes a phase 3 programme with CT-measured visceral fat. Sermorelin is often the entry point for sleep and recovery; tesamorelin is chosen when visceral fat is the specific goal.

CJC-1295 / Ipamorelin pairs a GHRH analogue with a ghrelin-receptor agonist, reaching the pituitary through two routes at once; it is the most commonly prescribed GH-axis combination for a general recovery and body-composition brief. Tesamorelin is a single-route product with the stronger trial record for one endpoint. Tesamorelin + Ipamorelin exists for people who want tesamorelin's GHRH signal with the second route added.

The same active peptide, not the same product. Egrifta is manufactured under a biologics licence, was tested at 2 mg daily in people with HIV-associated lipodystrophy, and is approved for that indication alone. Compounded tesamorelin is prepared by a licensed pharmacy to your prescription, at a dose and schedule your physician sets, and is not FDA approved. The trial results belong to the approved product; the compounded version borrows the mechanism, not the data.