What it is
Tesamorelin is a synthetic analog of the full 44-amino-acid human growth hormone-releasing hormone (GHRH), with a trans-3-hexenoic acid group added at its N-terminal tyrosine. It was developed by Theratechnologies under the code TH9507 and approved by the FDA in 2010, on the strength of two phase 3 trials, for excess abdominal fat in adults with HIV-associated lipodystrophy. Later investigator-led trials examined liver fat and cognition.
Mechanism of action
Tesamorelin binds the GHRH receptor on pituitary somatotroph cells and stimulates the pituitary to make and release its own growth hormone (GH), which raises circulating insulin-like growth factor 1 (IGF-1). Native GHRH is broken down quickly in plasma, mainly by dipeptidyl peptidase-4 (DPP-4) cleavage at the N-terminus; the hexenoyl group on tesamorelin's N-terminal tyrosine is thought to hinder that cleavage. Because it acts upstream of GH, the GH it releases comes from the body's own pituitary rather than from injected hormone. GH promotes the breakdown of stored fat, and visceral (deep abdominal) fat appears especially responsive: in the phase 3 program visceral fat fell while subcutaneous and limb fat were reported as preserved. IGF-1 rose 81% in the first phase 3 trial (Falutz et al. 2007) and 117% in a cognition trial (Baker et al. 2012). How these hormone changes relate to liver fat and brain function is still being studied.
What it’s most studied for
Tesamorelin's main research use is reduction of visceral fat in people with HIV who developed abdominal fat accumulation while on antiretroviral therapy, the population in which its phase 3 trials and FDA approval were based. Because excess visceral fat often travels with fatty liver, investigators then tested it for liver fat in people with HIV, including a 12-month multicentre trial in non-alcoholic fatty liver disease. A separate line of work at the University of Washington examined whether raising GH and IGF-1 with tesamorelin affects cognition in healthy older adults and in adults with mild cognitive impairment. It is not approved as a weight-loss drug.
Notable findings
Each finding carries the species or population it was observed in and the dose that study used. Doses are reported as research context, exactly as published. They are not guidance.
Phase 3 trial: visceral fat in HIV
Falutz et al. (2007) randomized 412 adults with HIV and abdominal fat accumulation, 86% of them men, to tesamorelin or placebo. Over 26 weeks, CT-measured visceral fat fell 15.2% with tesamorelin and rose 5.0% with placebo, and triglycerides fell by 50 mg/dL versus a 9 mg/dL rise. IGF-1 rose 81.0%, glucose measures did not differ between groups, and peripheral edema, myalgia, hypoesthesia, paresthesia, rash and injection-site reactions were the drug-related events, each in under 10% of patients.
- Dose studied
- 2 mg subcutaneously once daily for 26 weeks, adults with HIV and abdominal fat accumulation (phase 3 trial)
[1] Falutz J et al. · 2007 · PMID 18057338 ↗
Pooled phase 3 analysis of 806 patients
Falutz et al. (2010) pooled the two phase 3 trials, in which 806 adults with HIV and excess abdominal fat on antiretroviral therapy were randomized 2:1 to tesamorelin (n=543) or placebo (n=263). Visceral fat fell significantly more with tesamorelin than with placebo at 26 weeks, and triglycerides also fell. Adverse event rates were reported as similar between the groups.
- Dose studied
- 2 mg subcutaneously once daily for 26 weeks, followed by a 26-week safety extension (adults with HIV, phase 3 trials)
[3] Falutz J et al. · 2010 · PMID 20554713 ↗
Visceral fat returned after stopping
Falutz et al. (2008) extended the first phase 3 trial for another 26 weeks: patients on tesamorelin were re-randomized to continue (n=154) or switch to placebo (n=50), and placebo patients switched to tesamorelin (n=111). The visceral-fat reduction was maintained with continued treatment, while visceral fat reaccumulated after tesamorelin was stopped. Adverse event rates in the extension were comparable with the first phase, and glucose changes over 52 weeks were not clinically significant.
- Dose studied
- 2 mg subcutaneously once daily, adults with HIV and abdominal fat accumulation, 52 weeks in total (26-week trial plus 26-week extension)
[2] Falutz J et al. · 2008 · DOI 10.1097/QAD.0b013e32830a5058 ↗
Liver fat in HIV-associated fatty liver
Stanley et al. (2019) enrolled 61 adults with HIV and a hepatic fat fraction of 5% or more on MR spectroscopy. After 12 months, liver fat fell more with tesamorelin than with placebo, an absolute difference of 4.1 percentage points (a 37% relative reduction from baseline), and 35% of the tesamorelin group versus 4% of the placebo group reached a hepatic fat fraction below 5%. The trial also reported less fibrosis progression with tesamorelin.
- Dose studied
- 2 mg once daily for 12 months, followed by a 6-month open-label phase (adults with HIV and fatty liver, randomized trial)
[5] Stanley TL et al. · 2019 · PMID 31611038 ↗
Liver and visceral fat, single-center trial
Stanley et al. (2014) randomized 50 antiretroviral-treated adults with HIV and abdominal fat accumulation at Massachusetts General Hospital to tesamorelin (n=28) or placebo (n=22) for 6 months. The authors reported a modest but statistically significant decrease in liver fat with tesamorelin, which was associated with the reduction in visceral fat, and described its clinical importance as uncertain.
- Dose studied
- 2 mg subcutaneously once daily for 6 months (adults with HIV, randomized trial)
[4] Stanley TL et al. · 2014 · PMID 25038357 ↗
Cognition in older adults and MCI
Baker et al. (2012) enrolled 152 adults aged 55 to 87, 66 of whom had mild cognitive impairment; 137 completed the study. The trial reported a cognitive benefit of similar size in both groups in the intent-to-treat analysis (P = 0.03), with a positive effect on executive function (P = 0.005) and a trend for verbal memory (P = 0.08). IGF-1 rose 117% and stayed within the physiological range, and mild adverse events were reported by 68% of the tesamorelin group versus 36% of the placebo group.
- Dose studied
- 1 mg subcutaneously once daily for 20 weeks (adults aged 55 to 87, randomized trial)
[6] Baker LD et al. · 2012 · PMID 22869065 ↗
Study quality
The evidence for tesamorelin's approved use is strong: two randomized, double-blind, placebo-controlled phase 3 trials (806 patients pooled) supported FDA approval in 2010. Those trials enrolled only adults with HIV and abdominal fat accumulation, and their main outcome was CT-measured visceral fat, not heart disease or survival; at approval, FDA noted that effects on cardiovascular risk had not been studied. In the extension phase, visceral fat reaccumulated after treatment stopped. The liver-fat and cognition trials were well controlled but small (50 to 152 participants), and liver fat and cognition are not approved uses. Commonly reported adverse events include joint pain, injection-site reactions, edema and muscle pain. The prescribing information warns of glucose intolerance (5% versus 1% reaching HbA1c of 6.5% or more by week 26 in trials), hypersensitivity reactions in 4% of trial patients, fluid retention, and sustained IGF-1 elevation whose long-term effects are unknown.
References
- 1Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine. PMID 18057338
- 2Long-term safety (52 weeks) and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS. DOI 10.1097/QAD.0b013e32830a5058
- 3Effects 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 and Metabolism. PMID 20554713
- 4
- 5Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. The Lancet HIV. PMID 31611038
- 6
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