Tesamorelin (visceral fat use)

Tesamorelin is human GHRH(1-44) with a hexenoyl group attached to the N-terminus, a modification that protects it from dipeptidyl peptidase IV cleavage and extends its usable life without altering receptor binding. It stimulates the pituitary GHRH receptor to release growth hormone in a pattern that preserves normal pulsatility and negative feedback, which is why it does not produce the flat, supraphysiological exposure of injected recombinant GH. GH in turn drives lipolysis, and visceral adipose tissue is unusually GH-responsive because of its high density of GH receptors and beta-adrenergic sensitivity - which is the mechanistic explanation for why the visceral compartment shrinks while subcutaneous fat changes far less. The trade-off, well documented in the registration trials, is a reduction in insulin sensitivity, and visceral fat returns within roughly six months of stopping.

Targets: GHRH receptor (GHRHR), Pituitary somatotrophs, Growth hormone / IGF-1 axis, Visceral adipose tissue lipolysis

• · 1.4 mg daily — 0.35 mL of a 2 mg vial reconstituted with 0.5 mL of Sterile Water for Injection, prepared fresh and injected immediately. The 2 mg vial strength is not the dose. The pivotal trials used 2 mg daily of the original EGRIFTA formulation; EGRIFTA SV's 1.4 mg is the bioequivalent dose of the newer formulation.
• · Egrifta WR is 1.28 mg daily from an 11.6 mg vial reconstituted once weekly with 1.3 mL of diluent, giving roughly 8.9 mg/mL. Work the draw volume out from that concentration rather than memorising a millilitre figure, and store the reconstituted vial at room temperature for up to seven days.
• · Some people run 1 mg daily to reduce cost and side effects, but there is no evidence 1 mg matches the labelled dose. The ceiling is 1.4 mg, the labelled Egrifta SV dose — not the 2 mg vial strength. The original 2 mg regimen belongs to the discontinued Egrifta formulation and is a 43% overdose relative to any tesamorelin product currently on the market.

Work out your exact syringe units →

• very commonInjection-site erythema, pruritus and pain— The most frequent complaint in the trials; rotate abdominal sites.
• commonArthralgia and peripheral oedema— Classic GH-mediated fluid effects.
• commonReduced insulin sensitivity / raised glucose— Documented in the registration trials. Meaningful if you already have impaired glucose tolerance.
• commonMyalgia and paraesthesia
• uncommonCarpal tunnel syndrome— Dose-related GH effect; usually resolves on stopping.
• uncommonHypersensitivity reaction including rash and urticaria— Anti-tesamorelin antibodies develop in a substantial minority but rarely affect efficacy.
• uncommonFluid retention causing weight gain— Can mask the fat loss on the scale in the first weeks.

• Active malignancy - the label requires that any active malignancy be evaluated before starting, since GH is permissive for growth.
• Disruption of the hypothalamic-pituitary axis from surgery, radiation, trauma or tumour.
• Pregnancy - it is contraindicated because visceral fat reduction offers no benefit and GH exposure is unstudied.
• Known hypersensitivity to tesamorelin or mannitol.

• redundantsomatropin — Both raise GH exposure; combining them adds side effects without a rationale, and tesamorelin works by stimulating a pituitary that GH therapy suppresses.
• synergyipamorelin — GHRH plus GHRP is the standard amplification pairing, though tesamorelin's evidence base was built as monotherapy.
• synergysemaglutide — Increasingly stacked for visceral fat plus overall weight loss; no interaction trial exists, and both affect glucose handling in opposite directions.
• cautioninsulin-analogues — Tesamorelin worsens insulin sensitivity, so insulin requirements can rise.

• · Fasting glucose and HbA1c at baseline and periodically - this is the one lab that genuinely matters here.
• · IGF-1 levels; the label advises caution if IGF-1 rises persistently above the normal range.
• · Waist circumference or CT visceral adipose area if you want to know whether it is actually working.
• · Current age-appropriate cancer screening before starting.

FDA-approved (Egrifta, Egrifta SV, and Egrifta WR since March 2025) for excess visceral abdominal fat in adults with HIV-associated lipodystrophy. Any other use is off-label. Prohibited at all times in sport by WADA.

• Falutz et al. 2007, New England Journal of Medicine - tesamorelin and visceral adipose tissue in HIV lipodystrophy (trial)
• EGRIFTA WR (tesamorelin) FDA prescribing information (label)
• Pooled phase 3 analyses of tesamorelin visceral fat reduction and glucose effects (trial)
• Studies of tesamorelin for hepatic fat reduction in people with HIV (trial)

Tesamorelin is the only compound in this entire class with phase 3 data showing a body-composition endpoint, and the mechanism is worth understanding precisely because it explains why the effect is so specific to visceral fat. It is a GHRH analogue: it binds the GHRH receptor on pituitary somatotrophs, which is Gs-coupled, so adenylate cyclase raises cAMP, PKA activates, CREB is phosphorylated, and GH is both synthesised and released. Because it works through the physiological releasing pathway rather than bypassing it, the GH that results is pulsatile and remains subject to somatostatin and IGF-1 negative feedback - which is the whole safety argument for secretagogues over exogenous GH. The eight-minute half-life is not a flaw, it is the design: a sharp pulse, then silence, which is what the somatotroph axis expects. The resulting GH acts on adipose tissue through the GH receptor and JAK2-STAT5, and the key point is that visceral adipose tissue expresses more GH receptor and is more lipolytically responsive to GH than subcutaneous fat. GH activates hormone-sensitive lipase and adipose triglyceride lipase and inhibits lipoprotein lipase, and it does so preferentially where the receptors are densest. That is why the trials showed selective visceral fat loss rather than general fat loss. The two pivotal phase 3 trials, with 412 and 404 patients randomised 2:1 over 26 weeks with a 26-week extension, produced mean treatment differences in visceral adipose tissue of -31 cm2 and -21 cm2 versus placebo, with IGF-1 rising 107 and 108 ng/mL against essentially nothing on placebo. Stanley's JAMA trial extended the finding to liver fat. The cost side is visible in the same data: glucose intolerance developed in 5% of tesamorelin recipients versus 1% on placebo, which is GH counter-regulation doing exactly what GH does.

The most common practical failure is stopping. Falutz's long-term safety work showed that visceral fat returns when treatment ends - this is a suppressive therapy, not a cure, and the 26 weeks of gains reverse. Anyone planning an eight-week block is planning to spend a lot of money for a temporary effect. The second is watching the wrong number: the phase 3 endpoint was visceral adipose tissue, the treatment difference was -31 and -21 cm2, and scale weight barely moved. People conclude it is not working because they are weighing themselves. The third is the glucose signal, which is real and quantified at 5% versus 1%, and is the reason the label mandates glucose monitoring. Fourth, the two licensed formulations are not interchangeable by milligram - EGRIFTA SV is dosed at 2 mg and EGRIFTA WR at 1.4 mg for comparable exposure - so a grey-market vial labelled in milligrams tells you very little about what dose you are actually taking. And fifth, tesamorelin is a 44-residue peptide with an unusual N-terminal acyl modification, which is genuinely difficult to synthesise correctly; an unmodified GRF(1-44) would be degraded by DPP-4 within minutes and would do nothing.

1. 1 mgWeeks 1-2 — 1 mg daily as a tolerability ramp. This is not the licensed schedule - the label uses a fixed daily dose without titration - but starting low is how you find out whether arthralgia, peripheral oedema and injection-site reactions are going to be a problem before committing to the full dose.
2. 2 mgWeek 3 onward — 2 mg daily subcutaneously is the EGRIFTA SV dose used in the pivotal trials. The newer EGRIFTA WR formulation uses 1.4 mg daily, delivering comparable exposure from a reformulated product - so the milligram number alone does not tell you the exposure.
3. 2 mgWeek 26 assessment — The trials ran a 26-week main phase plus a 26-week extension. Twenty-six weeks is the point at which you decide whether it worked, using visceral fat and IGF-1 rather than the scale.

• Growth hormone releasing hormone receptor (GHRHR) — Full agonist at the native GHRH receptor; tesamorelin is GRF(1-44) with a stabilising N-terminal acyl group, so its receptor pharmacology is that of the endogenous ligand

  Gs-coupled: cAMP rise, PKA activation, CREB phosphorylation, GH synthesis and pulsatile release. Raised IGF-1 by 107-108 ng/mL in the phase 3 trials.

• Growth hormone receptor on visceral adipocytes (downstream) — Not a direct target of tesamorelin

  The released GH signals through JAK2-STAT5, activating hormone-sensitive lipase and adipose triglyceride lipase and suppressing lipoprotein lipase. Visceral fat is more GH-receptor-dense than subcutaneous fat, which is why the effect is regionally selective.

• Hepatic GH receptor — Downstream

  IGF-1 production, which drives the negative feedback that keeps the axis physiological, and also the liver fat reduction Stanley documented.

• Dipeptidyl peptidase-4 — Substrate rather than target - the trans-3-hexenoyl group exists to resist it

  The modification is why tesamorelin survives long enough to reach the pituitary despite an eight-minute half-life.

• Tesamorelin pivotal phase 3 study 1 (NCT00123253) Phase 3 · n=412 · 26 weeks

  Percent change in visceral adipose tissue in HIV-infected patients with lipodystrophy, randomised 2:1 to tesamorelin (n=273) or placebo (n=137), with a 26-week extension. Mean treatment difference in VAT was -31 cm2 (95% CI -39 to -24). IGF-1 rose 107 ng/mL versus -15 ng/mL on placebo.

• Tesamorelin pivotal phase 3 study 2 (NCT00435136) Phase 3 · n=404 · 26 weeks

  Replicate design: randomised 2:1 to tesamorelin (n=270) or placebo (n=126) with a 26-week extension. Mean treatment difference in VAT was -21 cm2 (95% CI -29 to -12). IGF-1 rose 108 ng/mL versus 3 ng/mL on placebo. Glucose intolerance developed in 5% on tesamorelin versus 1% on placebo.

• Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial Randomised controlled trial · 2014

  Reduction in hepatic fat alongside visceral fat, published in JAMA in 2014. Established that the effect extends to liver fat, not only to the visceral depot.

• Metabolic effects of a growth hormone-releasing factor in patients with HIV Phase 3 · 2007

  The New England Journal of Medicine report of tesamorelin's metabolic effects in HIV-associated abdominal fat accumulation, published 2007. The trial that established the compound.

The GH pulse occurs within minutes of injection and is over within an hour. IGF-1 rises measurably within two to four weeks toward the 107-108 ng/mL magnitude seen in the trials. Arthralgia, peripheral oedema, injection-site erythema and myalgia - the adverse effects reported at 5% or more - appear in the first weeks. The visceral fat effect was measured at 26 weeks, and that is the honest timeframe for judging it. On stopping, visceral fat returns over the following months.

The mechanistically coherent stack is tesamorelin with a GHRP - ipamorelin most sensibly - because the two act on different receptors and produce a larger pulse together than either alone: the GHRH analogue supplies the releasing signal while the GHRP raises somatotroph responsiveness and lowers somatostatin tone. That is the standard construction and it is sound. The interaction that actually matters clinically is with glucose: tesamorelin caused glucose intolerance in 5% of trial subjects, so combining it with anything else that raises glucose - other GH-axis drugs, glucocorticoids - compounds a documented risk. The pairing with a GLP-1 agonist is interesting and under-discussed, because the GLP-1 offsets the glycaemic cost while the tesamorelin defends against the lean mass loss and the visceral depot specifically. Nobody has tested it. Do not stack tesamorelin with exogenous growth hormone; you are supplying the releasing signal and the product simultaneously, negative feedback makes the GHRH analogue redundant, and you take the adverse effects of both.

Against everything else in this class, tesamorelin's distinction is straightforward: it has two pivotal phase 3 trials totalling over 800 patients, a licensed product, published pharmacokinetics and a quantified adverse-effect rate. Nothing else here except bimagrumab and apitegromab comes close. Against CJC-1295, the other GHRH analogue in common use: CJC-1295 with DAC has a much longer half-life and produces a sustained GH elevation, which sacrifices pulsatility - tesamorelin's eight-minute half-life preserves the pulsatile pattern the axis is built around, and that is a real physiological argument in its favour rather than a marketing one. Against exogenous growth hormone: tesamorelin works through the pituitary and remains subject to negative feedback, so it cannot produce the sustained supraphysiological levels that cause acromegalic changes, but it also cannot exceed what your pituitary can release. Against hexarelin and the GHRPs, tesamorelin acts on a different receptor and does not raise cortisol or prolactin. And against a GLP-1 agonist for fat loss, tesamorelin loses far less total weight but targets the visceral and hepatic depots specifically, which are the ones that carry the metabolic risk.

$250–$600/month. Grey-market tesamorelin runs roughly 50-100 USD per 10 mg vial, and 2 mg daily consumes about 60 mg a month. The licensed product is a specialty biologic priced an order of magnitude higher. The wide gap between those two prices is itself a reason to be sceptical about what is in the cheap vials.

• ?The sequence is marked unverified: tesamorelin is trans-3-hexenoyl-GRF(1-44) and the one-letter sequence given is human GHRH(1-44), which was not independently confirmed against a database entry in this session, and the acyl modification cannot be represented in one-letter code.
• ?Volume of distribution is reported in the label as 4.8 L/kg in healthy subjects after a 1.4 mg dose; this record leaves the absolute litre value null because it is weight-dependent and the schema expects an absolute figure.
• ?No numeric clearance value is published.
• ?All the efficacy data come from HIV-infected patients with lipodystrophy. Whether the same visceral fat effect occurs in a metabolically healthy person without lipodystrophy has not been established, and the population difference is not trivial.
• ?Protein binding was not reported in the label sections retrieved.
• ?Long-term safety beyond 52 weeks is not well characterised, and the effect reverses on discontinuation.
• ?What is actually in grey-market tesamorelin vials is unknown; the N-terminal modification is the hard part of the synthesis and is invisible on a simple purity assay.

• EGRIFTA SV (tesamorelin) for injection - FDA prescribing information Theratechnologies Inc., DailyMed, U.S. National Library of Medicine

  Source of the pharmacokinetics - under 4% absolute subcutaneous bioavailability, 0.15 hour median tmax, 4.8 L/kg volume of distribution, approximately 8 minute elimination half-life - and of the phase 3 trial designs, VAT differences, IGF-1 changes and the 5% versus 1% glucose intolerance figure.

• Metabolic effects of a growth hormone-releasing factor in patients with HIV Falutz J, Allas S, Blot K, Potvin D, Kotler D, Somero M, Berger D, Brown S, Richmond G, Fessel J, Turner R, Grinspoon S, New England Journal of Medicine, 2007 · PMID 18057338

  The pivotal publication. This is the level of evidence that separates tesamorelin from everything else in this class.

• Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK, JAMA, 2014 · PMID 25038357

  Extends the effect to hepatic fat, which is arguably the more important outcome and is the basis for the interest in tesamorelin for fatty liver disease generally.

• Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials Falutz J, Mamputu JC, Potvin D, Moyle G, Soulban G, Loughrey H, Marsolais C, Turner R, Grinspoon S, Journal of Clinical Endocrinology and Metabolism, 2010 · PMID 20554713

  The pooled analysis across both pivotal trials - the best single summary of the efficacy and safety data.

• Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation Falutz J, Allas S, Mamputu JC, Potvin D, Kotler D, Somero M, Berger D, Brown S, Richmond G, Fessel J, Turner R, Grinspoon S, AIDS, 2008 · PMID 18690162

  The 52-week safety data, including what happens when treatment stops - the visceral fat comes back.

• The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV Adrian S, Scherzinger A, Sanyal A, Lee E, Bass NM, Grinspoon S, Falutz J, Mamputu JC, Marsolais C, Brown TT, Erlandson KM, Journal of Frailty & Aging, 2019 · PMID 31237318

  Directly relevant to the body-composition use case: tesamorelin reduced intramuscular fat and increased muscle area, not only visceral fat.

• Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors Russo SC, et al., AIDS, 2024 · PMID 38905488

  Recent data in the modern treatment era, showing the effect holds in patients on contemporary antiretroviral regimens.