Tesamorelin is a synthetic analogue of growth hormone-releasing hormone (GHRH), the hypothalamic peptide that tells the pituitary gland to release growth hormone. It keeps all 44 amino acids of the human hormone and adds a single small acyl group at the front[1]. Under the brand name Egrifta it is approved in the United States for one narrow purpose: reducing excess abdominal fat in adults with HIV whose fat distribution has been changed by the disease and its treatment[1].
Among the peptides that raise growth hormone, tesamorelin is the one that went through full drug development, with two phase 3 trials and more than 800 patients[2]. That makes it a useful reference point. The trials show a real but modest effect on fat inside the abdomen, an effect that fades once injections stop, and side effects that follow directly from higher growth hormone[1][3]. The FDA and European regulators reached different benefit–risk assessments of the same data[4].
| Type | Synthetic analogue of human GHRH |
|---|---|
| Other names | TH9507; brands Egrifta, Egrifta SV, Egrifta WR |
| Length | 44 amino acids plus an N-terminal trans-3-hexenoyl group |
| Molecular weight | 5135.9 Da |
| Given as | Injection under the skin of the abdomen, once daily |
| Half-life in blood | About 11 minutes |
| Regulatory status | Approved in the United States (2010); authorised in Canada in 2014, registrations since cancelled; EU application withdrawn (2012) |
| Sport | Prohibited by WADA (class S2, GHRH analogues) |
What the molecule is
Tesamorelin has the same 44-amino-acid sequence as natural human GHRH. The only addition is a trans-3-hexenoyl group, a six-carbon chain with a trans double bond at position 3, attached to the tyrosine at the N-terminus[1][5]. Natural GHRH is broken down quickly in blood, and the cap was added to make the molecule more resistant to enzymatic degradation[6]. It is a small change compared with modern peptide drugs such as retatrutide, which carry non-standard amino acids and a fatty acid chain for binding to albumin.
Even with the cap, tesamorelin does not last long. After an injection under the skin, it reaches its peak in blood in about 9 minutes. For the original 2 mg formulation, less than 4% of the injected dose reached the circulation; for the current 1.28 mg formulation, which gives similar blood levels, the half-life is about 11 minutes[1]. This short presence is enough, because the peptide only needs to trigger the pituitary, and its effect is measured downstream, in growth hormone and in insulin-like growth factor 1 (IGF-1).
How it works
In laboratory tests tesamorelin binds and activates the human GHRH receptor about as strongly as the natural hormone[1]. The receptor sits on somatotroph cells in the pituitary, which respond by making and releasing growth hormone in pulses. Growth hormone breaks down fat and builds tissue; many of its effects run through IGF-1, which the liver makes in response to it[1].
The difference from injecting growth hormone itself is that the body still controls the output. Tesamorelin increases the pituitary's own pulsatile secretion instead of replacing it[6]. In the trials it raised IGF-1 by roughly 105 to 120 ng/mL more than placebo over 26 weeks, while other pituitary hormones (TSH, LH, ACTH and prolactin) did not change in a clinically significant way[1]. Because it works through the pituitary, it is contraindicated in people whose hypothalamic-pituitary axis has been disrupted by surgery, tumours, irradiation or head trauma[1].
What the trials found
The approval rests on two randomised, double-blind trials in people with HIV who were on stable antiretroviral therapy and had a large waist. Together they enrolled 816 patients; the first was published in 2007[7], and a pooled analysis of both followed in 2010[2]. Patients injected 2 mg of tesamorelin or placebo every day for 26 weeks. The main outcome was the change in visceral fat, the fat around the organs inside the abdomen, measured by CT at the level of the lower spine[3].
| Outcome | Trial 1 | Trial 2 |
|---|---|---|
| Visceral fat, relative | −20% | −12% |
| Visceral fat, cm² on CT | −31 | −21 |
| Waist, cm | −2 | −1 |
| Body weight, kg | −0.4 | +0.2 |
Differences between groups from the FDA prescribing information[1]. Patients started with about 180 cm² of visceral fat and a waist of about 104 cm. The change in body weight was not statistically significant in either trial.
Visceral fat fell, while fat under the skin of the abdomen barely changed[2]. Trunk fat fell by about 1 kg and lean body mass rose by about 1.2 to 1.3 kg, so body weight stayed the same[1]. Triglycerides and the ratio of total to HDL cholesterol improved slightly[2]. A 2026 meta-analysis of four placebo-controlled trials with 909 patients reached similar figures: visceral fat −21 cm², waist −1.6 cm, trunk fat −1.2 kg and lean mass +1.4 kg compared with placebo[6].
The effect lasts only as long as the injections. In both trials, patients who had taken tesamorelin for 26 weeks were randomised again to continue or to switch to placebo. Those who continued kept their lower visceral fat for another 26 weeks. Those who stopped regained it: their visceral fat rose by 16 to 22% over the next six months, close to where it started[1][3].
Two smaller trials from Massachusetts General Hospital looked at fat in the liver. In 50 patients treated for six months, tesamorelin lowered visceral fat by 42 cm² more than placebo and also reduced liver fat modestly[8]. In a 12-month trial of 61 patients with non-alcoholic fatty liver disease, liver fat fell by 4.1 percentage points more than with placebo, a relative reduction of 37%, and liver fat dropped below the 5% threshold in 35% of treated patients versus 4% on placebo[9]. In the second trial, among patients with liver biopsies at the start and end, fibrosis (scarring) progressed in 2 of 19 on tesamorelin (10.5%) and 9 of 24 on placebo (37.5%), but existing fibrosis did not improve[9]. Neither trial was large or long enough to establish long-term clinical benefits, and the authors called for further study[9].
How regulators judged it
The FDA approved tesamorelin in 2010[1]. The label is unusually explicit about what the drug does not do: long-term cardiovascular safety has not been established, it is not indicated for weight loss because its effect on weight is neutral, and there is no evidence that it helps patients keep taking their HIV medicines[1]. In 2025 a newer formulation, Egrifta WR, was approved at a lower dose of 1.28 mg once daily, based on showing the same exposure in blood as the original 2 mg dose; the two formulations are not interchangeable[1].
In Europe the outcome was different. In 2012 the company withdrew its application after the EMA's committee for human medicines gave the provisional view that the drug could not be approved[4]. The committee's reasons were specific:
- It is hard in practice to tell abdominal fat caused by HIV lipodystrophy from ordinary obesity, and the proposed cut-off of 130 cm² of visceral fat was not well supported.
- The reduction in fat had not been shown to bring actual health benefits to patients.
- Patients in the trials were heavier and had more abdominal fat than typical European patients with HIV.
- IGF-1 rose considerably in many treated patients, which the committee regarded as a major safety concern, and there were no long-term safety data for a drug meant to be used long term[4].
Health Canada authorised tesamorelin in 2014[10]. Both Canadian registrations of Egrifta have since been cancelled, in 2022 and 2023[10]. In 2016 the Canadian health technology agency, CADTH, reviewed the evidence. It found that the reductions in visceral fat (12 to 20%) and waist (1.3 to 1.8 cm) exceeded the minimum that Health Canada had set as clinically relevant, but that their importance was unclear: body image did not improve consistently, and quality of life did not improve at all[3]. CADTH also noted that more than half of the patients in the phase 3 trials took older protease inhibitor-based regimens, which are linked to abdominal fat gain, while current HIV treatment relies mostly on integrase inhibitors[3].
Side effects and risks
In the 26-week trials, 543 patients received tesamorelin and 263 received placebo. The side effects that appeared more often with tesamorelin are those expected from more growth hormone and from daily injections[1]:
| Side effect | Tesamorelin | Placebo |
|---|---|---|
| Injection site reactions | 17% | 6% |
| Joint pain | 13% | 11% |
| Pain in arms or legs | 6% | 5% |
| Muscle pain | 6% | 2% |
| Swelling of the legs | 6% | 2% |
| Tingling or numbness | 5% | 2% |
Selected rows from table 1 of the FDA prescribing information[1]. "Tingling or numbness" is paresthesia; hypoesthesia was reported in 4% and 2%.
Fluid retention, joint pain and carpal tunnel syndrome are associated with increased growth hormone activity and often resolve after treatment is stopped[1]. Allergic-type reactions such as rash and itching occurred in 4% of treated patients[1]. The label also advises considering stopping tesamorelin in critically ill patients, because pharmacological doses of growth hormone have been linked to higher mortality in acute critical illness, and checking people with diabetes for new or worsening retinopathy[1]. More patients stopped tesamorelin than placebo because of side effects, although in the 2026 meta-analysis the difference fell just short of statistical significance[6].
Three risks need monitoring:
- IGF-1. After 26 weeks, 47% of treated patients had IGF-1 more than two standard deviations above the normal mean for their age, and 36% more than three. The effects of long-lasting high IGF-1 are unknown, and the label advises regular checks and stopping treatment if the levels stay high[1].
- Blood sugar. Diabetes (HbA1c of 6.5% or higher) developed in 5% of treated patients and 1% on placebo[1]. In the two smaller MGH trials, glucose did not differ significantly from placebo over the whole treatment period, although in one of them fasting glucose rose during the first two weeks[8][9].
- Cancer. Because growth hormone and IGF-1 promote cell growth, tesamorelin is contraindicated in active cancer, and the label asks for careful evaluation in people with a history of it[1]. The trials were too short and too small to measure any effect on cancer risk[3].
About half of the treated patients developed antibodies against tesamorelin, and in about 60% of them the antibodies also recognised the body's own GHRH. In the trials the antibodies did not reduce the effect on visceral fat or IGF-1[1]. Tesamorelin is also contraindicated in pregnancy[1].
Beyond the approved use
Because tesamorelin raises growth hormone, it is often mentioned alongside other peptides for fat loss, body composition and ageing. The evidence outside HIV-associated fat gain is limited.
- Weight loss. In the phase 3 trials body weight did not change, because the loss of fat was offset by a gain in lean mass[1]. The FDA label states plainly that tesamorelin is not indicated for weight loss[1].
- Muscle. Lean body mass rose by 1.2 to 1.4 kg[1][6]. The trials measured it by body scans; they did not test strength or physical performance.
- Memory and thinking. One randomised trial gave 152 adults aged 55 to 87 either tesamorelin 1 mg or placebo every evening for 20 weeks; 137 completed it. Scores on a combined cognitive test improved slightly more with tesamorelin, mainly in executive function, both in healthy older adults and in those with mild cognitive impairment. Side effects were reported by 68% of treated participants and 36% on placebo, and the authors described the results as a reason for longer trials, not as a treatment[5].
- Fatty liver. The 12-month MGH trial is the strongest result outside visceral fat, but it was small and limited to people with HIV[9].
Tesamorelin is prohibited in sport at all times. WADA lists it by name among GHRH analogues in class S2, together with sermorelin and CJC-1295[11].
In short
- Tesamorelin is human GHRH, all 44 amino acids, with a hexenoyl cap added to slow its breakdown.
- It raises the body's own growth hormone and IGF-1; it lasts only minutes in blood.
- In two phase 3 trials with 816 people with HIV-associated lipodystrophy it reduced visceral fat by 12 to 20% over 26 weeks without changing body weight, and the fat came back after it was stopped.
- The FDA approved it in 2010 for this narrow use; the EMA committee judged that the benefit had not been shown to outweigh the risks, mainly high IGF-1 and no long-term data.
- Evidence for other uses consists of a few small trials; it is not a weight loss drug, and WADA bans it in sport.
References
- U.S. Food and Drug Administration (2025). EGRIFTA WR (tesamorelin) for injection, for subcutaneous use: full prescribing information. Revised 3/2025. accessdata.fda.gov (PDF)
- Falutz J, Mamputu JC, Potvin D, Moyle G, Soulban G, Loughrey H, Marsolais C, Turner R, Grinspoon S (2010). 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. Journal of Clinical Endocrinology & Metabolism 95(9):4291–4304. DOI: 10.1210/jc.2010-0490
- CADTH Common Drug Review (2016). Clinical review report: tesamorelin (Egrifta). Ottawa: Canadian Agency for Drugs and Technologies in Health. ncbi.nlm.nih.gov
- European Medicines Agency (2012). Questions and answers on the withdrawal of the marketing authorisation application for Egrifta (tesamorelin). EMA/CHMP/475021/2012. ema.europa.eu (PDF)
- Baker LD, Barsness SM, Borson S, Merriam GR, Friedman SD, Craft S, Vitiello MV (2012). Effects of growth hormone–releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Archives of Neurology 69(11):1420–1429. DOI: 10.1001/archneurol.2012.1970
- Ditta AM, Naeem RM, Sami MM, Rafey MA, Ali H, Amjad MW, Jahangir F, Rizvi KA, Mohammad F, Abu Dawood H, Suleman M, Saddique MN (2026). Efficacy and safety of tesamorelin in people living with HIV (PLWH) with lipodystrophy: a systematic review and meta-analysis. Journal of the International Association of Providers of AIDS Care 25:1–16. DOI: 10.1177/23259582261475549
- Falutz J, Allas S, Blot K, Potvin D, Kotler D, Somero M, Berger D, Brown S, Richmond G, Fessel J, Turner R, Grinspoon S (2007). Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine 357(23):2359–2370. DOI: 10.1056/NEJMoa072375
- Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK (2014). Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA 312(4):380–389. DOI: 10.1001/jama.2014.8334
- Stanley TL, Fourman LT, Feldpausch MN, et al. (2019). Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV 6(12):e821–e830. DOI: 10.1016/S2352-3018(19)30338-8
- Health Canada (2014). Summary Basis of Decision for Egrifta (tesamorelin). Notice of Compliance 29 April 2014; product information including DIN status. dhpp.hpfb-dgpsa.ca
- World Anti-Doping Agency (2025). The 2026 Prohibited List, International Standard. wada-ama.org