How does it work?
The body makes its own GHRH in the brain, as a signal to the pituitary gland to release growth hormone. Tesamorelin mimics this signal and causes the pituitary to release the body's own growth hormone in natural pulses, rather than supplying growth hormone directly from outside. Researchers have been particularly interested in how this rise in growth hormone and IGF-1 affects the way the body stores fat, especially the deep fat around the organs in the abdominal cavity (visceral fat).
Technical mechanism
Synthetic GHRH(1-44) analogue. Acts on the pituitary gland, producing pulsatile release of the body's own growth hormone and a subsequent rise in IGF-1. Reduced visceral fat has been reported in clinical studies.
What is being researched?
- Deep abdominal fat (visceral fat) in people with HIV-associated lipodystrophy
- Fat in the liver and non-alcoholic fatty liver disease (NAFLD)
- Metabolic markers such as blood fats (triglycerides) and cholesterol
- Cognitive function and memory in older adults
- Levels of the body's own growth hormone and IGF-1
About the evidence: For tesamorelin there are several large, randomised, placebo-controlled studies in humans, and the substance is approved as a medicine in the USA for one specific condition. Note, however, that almost all of the large studies were carried out in people with HIV with abnormal fat distribution; how well the results transfer to healthy people has been investigated far less. The content here describes what the research has looked at, and is neither health advice nor a recommendation for use.
Research profile
Studies and sources
The links go to independent research databases (PubMed, PubMed Central, ClinicalTrials.gov). The studies are in English and open in a new tab.
Visceral abdominal fat in HIV lipodystrophy
The largest and best-known studies on tesamorelin have investigated whether the substance reduces the deep fat around the organs in people with HIV who have developed abnormal fat distribution. These studies are the basis on which the substance was approved as a medicine.
- Metabolic effects of a growth hormone-releasing factor in patients with HIV Clinical (human)PubMed· 2007
In this study, 412 HIV patients with accumulated abdominal fat received daily injections of either tesamorelin or a dummy treatment (placebo) for 26 weeks. Inner abdominal fat (visceral fat) fell by just over 15% in the tesamorelin group, while it increased in the placebo group. Blood fats (triglycerides and cholesterol ratio) also improved, and IGF-1 levels rose. Blood sugar did not change significantly. More people in the tesamorelin group nevertheless stopped because of side effects.
- Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension Clinical (human)PubMed· 2010
In this 12-month study of 404 HIV patients with abdominal fat, participants received tesamorelin or placebo. Inner abdominal fat fell by around 11% after 6 months and by about 18% in those who continued for 12 months, while placebo produced almost no change. Waist measurement and perceived body image improved, and IGF-1 rose, with no change in blood sugar. When treatment was switched to placebo, the abdominal fat quickly returned. The medicine was well tolerated.
- Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat Clinical (human)PubMed· 2015
This analysis of two phase 3 studies looked at which HIV patients reduced inner abdominal fat most with tesamorelin. Patients with metabolic syndrome, high triglycerides or white skin colour had the greatest chance of responding after 6 months. After 3 months the researchers could not identify reliable early predictors. The chance of reaching an abdominal fat level below 140 cm² was nearly four times higher with tesamorelin than with placebo. The study therefore describes traits associated with a better response.
- Growth hormone-releasing factor agonists for the treatment of HIV-associated lipodystrophy ReviewPubMed· 2010
This review article discusses growth hormone-releasing factor analogues as a possible treatment for HIV-related lipodystrophy, in which the body's fat distribution and metabolism are disturbed. Tesamorelin is highlighted as the most promising, since in two phase 3 studies it reduced excess inner abdominal fat in HIV patients. The authors stress that more long-term studies are needed to clarify long-term safety and whether the treatment can reduce cardiovascular risk.
Liver fat and fatty liver disease (NAFLD)
More recent studies have explored whether the reduction in abdominal fat is also linked to less fat in the liver itself, and what this may mean for markers of liver health.
- Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial Clinical (human)PubMed· 2014
In this study, 50 HIV patients with abdominal fat received tesamorelin or placebo for 6 months. Tesamorelin reduced both inner abdominal fat and liver fat compared with placebo. Fasting blood sugar rose slightly in the first weeks, but after 6 months there was no clear difference in blood sugar between the groups. The authors describe this as a preliminary study and point out that more research is needed to understand the clinical significance and long-term effects.
- Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial Clinical (human)PubMed· 2019
In this study, 61 people with HIV and fatty liver (NAFLD) received tesamorelin or placebo for 12 months. Those who received tesamorelin had a greater reduction in liver fat, and after 12 months 35% in the tesamorelin group had less than 5% liver fat, compared with 4% in the placebo group. Blood sugar and long-term blood sugar (HbA1c) did not change differently between the groups. Some had local reactions at the injection site. The authors consider that more research on the liver is needed.
- Visceral fat reduction with tesamorelin is associated with improved liver enzymes in HIV Clinical (human)PubMed· 2017
This analysis of two phase 3 studies of 806 HIV patients with abdominal obesity investigated whether reduced inner abdominal fat was linked to liver values in the blood. Patients who responded to tesamorelin (at least 8% less abdominal fat) and who had raised liver enzymes at baseline saw a greater fall in the liver enzymes ALT and AST than those who did not respond. The improvement was maintained over 52 weeks, even in those who switched to placebo. Reduced abdominal fat was thus linked to better liver values.
Metabolic markers
Researchers have looked at whether changes in visceral fat are accompanied by changes in blood fats, cholesterol and other metabolic measurements.
- Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin Clinical (human)PubMed· 2012
This analysis of two phase 3 studies investigated whether reduced inner abdominal fat with tesamorelin was linked to better metabolism in HIV patients. Those who responded (at least 8% less abdominal fat) had a greater fall in triglycerides, better preserved blood sugar regulation and more favourable HbA1c and adiponectin than those who did not respond, over 52 weeks. The changes in blood fats and blood sugar were statistically associated with how much the abdominal fat fell.
Cognition and the brain
A separate line of research has explored whether increased GHRH signalling affects memory and thought processes in older adults, independently of HIV.
- Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial Clinical (human)PubMed· 2012
In this study, 152 older adults, some with mild cognitive impairment (MCI), received daily injections of tesamorelin (a stable GHRH variant) or placebo before bedtime for 20 weeks. The treatment had a favourable effect on thinking ability, particularly on so-called executive function, and similarly in both healthy participants and those with MCI. IGF-1 rose and body fat fell. Fasting insulin increased somewhat, within the normal range. The results are described as a positive but preliminary effect on cognition.
- Growth hormone-releasing hormone effects on brain γ-aminobutyric acid levels in mild cognitive impairment and healthy aging Clinical (human)PubMed· 2013
In this substudy, 30 older adults, some with mild cognitive impairment, received daily injections of tesamorelin (a GHRH variant) or placebo for 20 weeks, while the brain's signalling substances were measured with MR spectroscopy. After treatment, levels of the inhibitory signalling substance GABA had increased in several brain regions, and a substance linked to Alzheimer's (myo-inositol) was reduced in one region. Glutamate did not change. As in the main study, a favourable effect on thinking ability was seen.