Key takeaways
- Tesamorelin is the full 44-residue human GHRH sequence with a trans-3-hexenoyl group on the N-terminus, which protects it from dipeptidyl peptidase IV and extends its activity relative to native GHRH.
- Two phase 3 trials in people with HIV and abdominal fat accumulation recorded an average reduction in visceral adipose tissue of roughly 15 to 18 percent over 26 weeks, which reversed after discontinuation.
- Egrifta, and since 2025 Egrifta WR, are FDA-approved tesamorelin products for one indication: reduction of excess abdominal fat in adults with HIV-associated lipodystrophy. Research-grade tesamorelin is not the approved drug.
- Smaller controlled trials have examined liver fat in HIV-associated fatty liver disease and cognition in older adults; findings were encouraging but limited in size and duration.
Tesamorelin is the growth hormone-releasing hormone analogue with the largest clinical evidence base. Unlike sermorelin, which was withdrawn commercially, tesamorelin has been continuously approved in the United States since 2010, and its development program produced two placebo-controlled phase 3 trials, a series of mechanistic substudies, and follow-on trials in liver disease and cognition. That record makes it a useful reference point for GHRH-analogue research generally. It also creates a specific obligation for anyone writing about the research-grade material: the clinical findings belong to a pharmaceutical product with a defined formulation, manufacturing standard and indication, and none of that transfers to a research peptide simply because it shares the sequence. This note reviews the molecule, its mechanism, the trials that established it, the research that followed, and the boundaries of what the evidence supports.
The molecule
Native human GHRH is a 44-residue peptide with an amidated C-terminus. Its principal pharmacological weakness is a short half-life: the enzyme dipeptidyl peptidase IV (DPP-IV) cleaves the N-terminal tyrosine–alanine dipeptide within minutes of the hormone entering circulation, inactivating it. Tesamorelin, originally designated TH9507 by its developer Theratechnologies, addresses this directly. It retains the full GHRH(1-44)-NH2 sequence and adds a trans-3-hexenoyl group to the N-terminal tyrosine. The added hydrocarbon chain sterically hinders DPP-IV and slows degradation, so that the molecule persists long enough to produce a more sustained pituitary stimulus than native GHRH or sermorelin.1
Ferdinandi and colleagues published the nonclinical pharmacology and toxicology of TH9507 in 2007. In rats and dogs the compound stimulated GH release with potency comparable to or greater than native GHRH and with a longer duration of action; it showed no genotoxicity, and repeat-dose toxicology over 6 to 12 months in rats and dogs was consistent with the expected pharmacology of GH stimulation.1 This preclinical package is what allowed the compound to enter clinical development, and it remains the principal published source on tesamorelin’s animal pharmacology. The mechanism at the receptor is that of GHRH: binding to the GHRH receptor on pituitary somatotrophs, cyclic AMP elevation, and pulsatile release of growth hormone, with downstream elevation of IGF-1. As with all GHRH analogues, the response depends on an intact pituitary and is restrained by somatostatin and IGF-1 feedback. Our note on GH, GHRH and GHRP explains why this upstream action is pharmacologically distinct from exogenous GH.
| Property | Native GHRH(1-44) | Sermorelin | Tesamorelin |
|---|---|---|---|
| Length | 44 residues | 29 residues (1–29) | 44 residues (1–44) |
| Modification | None | None | N-terminal trans-3-hexenoyl group |
| DPP-IV susceptibility | High | High | Reduced |
| Plasma half-life | Minutes | Minutes | Longer; sustained GH stimulation |
| Regulatory status (US) | Not a drug product | Formerly approved (Geref), discontinued | Approved as Egrifta (2010), Egrifta WR (2025) |
The phase 3 trials and the approval
Tesamorelin was developed for a specific clinical problem. Some people living with HIV on antiretroviral therapy develop lipodystrophy, a redistribution of body fat that includes accumulation of visceral adipose tissue in the abdomen. This visceral fat is metabolically active and associated with cardiovascular and metabolic risk, and it had proven difficult to address. Because GH secretion is often blunted in this population and GH is lipolytic, particularly toward visceral fat, a GHRH analogue that restored pulsatile GH was a rational candidate.
Falutz and colleagues reported the first phase 3 trial in the New England Journal of Medicine in 2007. Over 26 weeks in more than 400 participants, daily tesamorelin reduced visceral adipose tissue, measured by computed tomography, by about 15 percent from baseline, while the placebo group gained about 5 percent. Triglycerides fell and the ratio of total to HDL cholesterol improved. IGF-1 rose, as expected. Glucose parameters were not significantly worsened over 26 weeks, which had been a concern given GH’s counter-regulatory effects on insulin.2 A second phase 3 trial replicated the design, and a pooled analysis of both trials with their 26-week extension phases, published in 2010, confirmed the visceral fat reduction, showed that it was maintained in participants who continued treatment to 52 weeks, and showed that it reversed toward baseline in participants switched to placebo after 26 weeks.3 The most common adverse events were injection-site reactions, arthralgia, peripheral edema and myalgia, consistent with GH stimulation.
On the strength of these trials, the FDA approved Egrifta (tesamorelin for injection) in November 2010 for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy. Dhillon’s review in Drugs summarized the approval package and the clinical pharmacology.4 In March 2025 the FDA approved Egrifta WR, a higher-concentration formulation of the same molecule that is still administered daily but requires reconstitution only once a week, for the same indication.5 The indication has not broadened: tesamorelin is not approved for weight management, for lipodystrophy of other causes, or for any use outside the HIV population in which it was studied.
The visceral fat came back when the drug stopped. That single observation defines both what tesamorelin does and what it does not do.
Approved drug vs. research compound
Egrifta and Egrifta WR are pharmaceutical products manufactured, tested and released under FDA oversight for one indication in one population. Research-grade tesamorelin shares the peptide sequence and nothing else: it has no approved indication, its composition is established by analytical testing rather than regulatory release, and the clinical findings above do not describe it. Wednesday’s third-party certificates for each lot are in the COA library.
Liver fat and fatty liver disease
Because visceral adiposity and hepatic steatosis are closely linked, investigators asked whether tesamorelin’s effect extended to the liver. Stanley and colleagues at Massachusetts General Hospital addressed this in a randomized trial published in JAMA in 2014. In 50 participants with HIV and abdominal fat accumulation, six months of tesamorelin reduced visceral fat as before and also reduced liver fat, measured by magnetic resonance spectroscopy, relative to placebo; the reduction in liver fat correlated with the reduction in visceral fat.6 The same group then ran a dedicated trial in HIV-associated nonalcoholic fatty liver disease, published in Lancet HIV in 2019. Over 12 months in 61 participants, tesamorelin reduced hepatic fat fraction by an absolute 4.1 percent compared with placebo, and a smaller proportion of tesamorelin-treated participants showed progression of fibrosis on paired liver biopsy.7 These are meaningful findings in a population with few options, but both trials were small, single-center and limited to people with HIV. Tesamorelin is not approved for liver disease.
Cognition in older adults
A separate line of research used tesamorelin as a tool to test whether restoring GHRH signaling affected cognition in aging. Baker and colleagues at the University of Washington reported a 20-week randomized placebo-controlled trial in 2012 involving 152 adults aged 55 to 87, some with mild cognitive impairment and some cognitively healthy. Daily tesamorelin was associated with improved performance on a composite of executive function tests, with a smaller effect on verbal memory, in both the healthy and impaired groups.8 These results have not been followed by a larger confirmatory trial, and the effect sizes, while statistically significant, were modest. They are best understood as evidence that GHRH signaling influences brain function in aging, which is a physiological finding, rather than as evidence for any clinical application.
Mechanistic and preclinical work
Beyond the toxicology program, preclinical study of tesamorelin specifically is limited; most animal work on GHRH agonists has used other stabilized analogues developed for extrapituitary targets. Granata and colleagues’ 2025 review of GHRH and its analogues places tesamorelin in that broader context: it is the analogue that reached the clinic for a pituitary-mediated metabolic indication, while other agonists have been studied in models of cardiac injury, pancreatic islet function and wound healing, and antagonists in cancer models.9 Where research-grade tesamorelin appears in the laboratory, it is typically as a well-characterized GHRH-receptor agonist with better stability than sermorelin, useful for probing the GHRH–GH–IGF-1 axis in models over longer intervals than the native peptide allows.
Safety signals in the clinical program
Two safety questions recur in the tesamorelin literature. The first is glucose: GH is counter-regulatory to insulin, and any sustained increase in GH secretion could impair glucose tolerance. In the phase 3 program, fasting glucose and hemoglobin A1c showed small increases that were not statistically different from placebo at 26 weeks, but a minority of participants developed impaired glucose tolerance, and the labeling advises monitoring.3 The second is IGF-1: sustained elevation of IGF-1 is a theoretical concern for malignancy, and the trials excluded participants with active cancer and monitored IGF-1 throughout. No signal emerged over the trial durations, but the trials were not designed or powered to detect long-term oncological risk. Both issues are addressed in the approved product’s labeling and are the reason it is prescribed with monitoring.
Where the evidence stops
The tesamorelin literature is stronger than that for any comparable peptide, and its limits should be described with the same precision. The phase 3 evidence is confined to adults with HIV and lipodystrophy; there are no phase 3 data in any other population. The liver and cognition findings come from single trials of modest size that have not been replicated at scale. The effect on visceral fat is dependent on continued administration and reverses on discontinuation. Long-term safety beyond 52 weeks in controlled settings is limited. And every one of these findings describes the approved pharmaceutical product, not research-grade material.
For a researcher, tesamorelin is a reference GHRH agonist with a well-documented clinical pharmacology and a stable structure. For a reader trying to understand the growth-hormone axis, its trials are the clearest demonstration available that stimulating endogenous GH pulses produces measurable, reversible, tissue-specific metabolic effects in humans. Neither of those statements extends the approved indication, and neither describes what a research peptide does in people. Our companion notes on sermorelin and CJC-1295 and ipamorelin cover the other GHRH analogues and the secretagogue class.
Frequently asked questions
What is tesamorelin?
Tesamorelin is a synthetic analogue of human growth hormone-releasing hormone. It has the full 44-residue GHRH sequence with a trans-3-hexenoyl group added to the N-terminus, which protects it from enzymatic breakdown. It stimulates the pituitary to release growth hormone in pulses.
Is tesamorelin FDA approved?
Yes, as Egrifta (2010) and Egrifta WR (2025), for one indication: reduction of excess abdominal fat in adults with HIV-associated lipodystrophy. It is not approved for any other use. Research-grade tesamorelin is not the approved drug.
What did the tesamorelin phase 3 trials show?
In two 26-week placebo-controlled trials in people with HIV and abdominal fat accumulation, tesamorelin reduced visceral adipose tissue by roughly 15 to 18 percent on average and improved triglycerides. The effect was maintained with continued treatment to 52 weeks and reversed after discontinuation.
Does tesamorelin affect liver fat?
Two small randomized trials in people with HIV found that tesamorelin reduced liver fat measured by MR spectroscopy and, in a 12-month trial, was associated with less fibrosis progression on biopsy. These findings have not been replicated in larger trials, and tesamorelin is not approved for liver disease.
How does tesamorelin differ from sermorelin?
Sermorelin is the unmodified first 29 residues of GHRH and is broken down within minutes. Tesamorelin is the full 44-residue sequence with an N-terminal modification that resists degradation, giving a longer-lasting stimulus. Sermorelin’s approved product was discontinued; tesamorelin remains approved for one indication.
References & further reading
- Ferdinandi ES, Brazeau P, High K, Procter B, Fournier S, Marleau S. Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic Clin Pharmacol Toxicol. 2007;100(1):49-58. doi:10.1111/j.1742-7843.2007.00008.x
- Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-2370. doi:10.1056/NEJMoa072375 / PMID 18057338
- Falutz J, Mamputu JC, Potvin D, et al. 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 with safety extension data. J Clin Endocrinol Metab. 2010;95(9):4291-4304. doi:10.1210/jc.2010-0490 / PMID 20554713
- Dhillon S. Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy. Drugs. 2011;71(8):1071-1091. doi:10.2165/11202240-000000000-00000
- Theratechnologies Inc. Theratechnologies receives FDA approval for EGRIFTA WR (tesamorelin F8) to treat excess visceral abdominal fat in adults with HIV and lipodystrophy. Press release, March 25, 2025. globenewswire.com
- Stanley TL, Feldpausch MN, Oh J, et al. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014;312(4):380-389. doi:10.1001/jama.2014.8334 / PMID 25038357
- Stanley TL, Fourman LT, Feldpausch MN, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019;6(12):e821-e830. doi:10.1016/S2352-3018(19)30338-8 / PMID 31611038
- Baker LD, Barsness SM, Borson S, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Arch Neurol. 2012;69(11):1420-1429. PMID 22869065
- Granata R, Leone S, Zhang X, et al. Growth hormone-releasing hormone and its analogues in health and disease. Nat Rev Endocrinol. 2025;21(3):180-195. doi:10.1038/s41574-024-01052-1 / PMID 39537825