Tesamorelin and Liver Fat: What a 12-Month Trial Found
Weight Loss & Metabolism Research
After twelve months on tesamorelin, 35% of people in a 2019 Lancet HIV trial had liver fat below the 5% line that defines fatty liver. On placebo, 4% did. Their body weight did not change. This article walks through that trial and the 2014 study that led to it, both run in people with HIV, and explains why tesamorelin is studied alongside ipamorelin.
View product →Findings
- Tesamorelin is a modified form of growth hormone releasing hormone (GHRH). Both liver trials enrolled people with HIV, the population in which tesamorelin has been developed.
- In the 2019 trial (61 people, 12 months, double-blind), liver fat fell 4.1 percentage points more than on placebo, a 37% relative reduction.
- 35% against 4% finished the year with liver fat under 5%.
- On repeat liver biopsy, fibrosis progressed in 2 people on tesamorelin (10.5%) against 9 on placebo (37.5%).
- Body weight, BMI and waist size did not change. The earlier 2014 trial in JAMA reported visceral fat down 34 cm² against up 8 cm² on placebo over six months.
Why liver fat, and why people with HIV
Non-alcoholic fatty liver disease (NAFLD, the condition now also called MASLD) is a substantial cause of illness in people with HIV, and when the 2019 trial was published there were no proven drug treatments for it in this population. Fat builds up inside liver cells and can bring inflammation and scarring (fibrosis) with it, and the 2019 paper notes that fibrosis may be more likely to progress in people with HIV.
Growth hormone sits at the centre of the story. The same authors point out that people with HIV have blunted growth hormone pulses, and that the degree of blunting closely tracks abdominal fat gain and weight gain. Tesamorelin restores the body’s own pulsatile growth hormone release, and it is thought to drive fat breakdown through that growth hormone while leaving the body’s feedback controls in place. In the United States it is approved to reduce excess abdominal fat in people with HIV, and both liver studies were run in that group.
The first signal: JAMA, 2014
The liver question was first tested in a double-blind trial at Massachusetts General Hospital in Boston. Stanley and colleagues randomised 50 men and women with HIV and abdominal fat accumulation, all on antiretroviral therapy, to tesamorelin (28) or placebo (22) for six months, with visceral fat and liver fat as the primary endpoints.
- Visceral fat: down 34 cm² on tesamorelin against up 8 cm² on placebo, a treatment effect of 42 cm² (P=.005).
- Liver fat: a median change of minus 2.0% on tesamorelin against plus 0.9% on placebo, measured as the lipid-to-water ratio (P=.003), a net treatment effect of 2.9 points.
The authors called it a preliminary study and said further work was needed on the clinical importance of the liver change. That is the question the next trial was built to answer.
The 12-month trial: Lancet HIV, 2019
Of 143 people screened at Massachusetts General Hospital and the US National Institutes of Health, 61 adults with HIV and liver fat of 5% or more, measured by magnetic resonance spectroscopy, were randomised to tesamorelin or an identical placebo for 12 months, followed by six months in which everyone received tesamorelin. Heavy drinkers and people with hepatitis B or active hepatitis C were excluded. Participants had a liver biopsy at the start and again at 12 months, scored by a pathologist who did not know who had received what.
The group started with substantial liver disease. Liver fat averaged 13.8%, ranging up to 45.4%; a third of participants already had steatohepatitis (NASH) on biopsy, and 43% had some degree of fibrosis.
| Measure at 12 months | What the trial reported |
|---|---|
| Liver fat, the primary endpoint | Fell 4.1 percentage points more than on placebo, a 37% relative reduction (p=0.018) |
| Liver fat under 5% | 35% on tesamorelin, 4% on placebo (p=0.0069) |
| Fibrosis progression on biopsy | 2 people (10.5%) on tesamorelin, 9 (37.5%) on placebo (P=0.04) |
| C-reactive protein, an inflammation marker | 4.7 mg/L lower than placebo (P=0.04) |
| ALT, in those with raised ALT at the start | Fell 29 U/L more than on placebo (P=0.03) |
| Visceral fat | Reduced against placebo; fat under the skin unchanged |
| Body weight, BMI and waist size | Unchanged |
| Fasting glucose and HbA1c | Unchanged |
The authors wrote that tesamorelin was, at that point, the only agent shown to reduce liver fat and prevent fibrosis progression specifically in people with HIV. They also flagged the placebo arm as a finding in itself: more than a third of the placebo group saw fibrosis advance within a single year. Fibrosis already present at the start did not improve compared with placebo, and the authors call for longer studies of liver tissue.
Vistara Labs stocks Tesamorelin as a lyophilised research material, shipped from within Canada to every province.
Liver fat came down while weight stayed put
The detail that makes this trial stand out is what did not change. Body weight, BMI and waist size held steady across the year, four-day food records and activity questionnaires showed no shifts, and lean mass rose modestly. Liver fat still fell, and visceral fat fell with it while fat under the skin did not. That pattern fits the mechanism the authors describe: restored growth hormone pulses driving fat breakdown, concentrated in the fat around the organs and in the liver rather than across the whole body. For research on liver and visceral fat that is not simply a weight-loss story, Tesamorelin is the compound with this trial record.
Tesamorelin and ipamorelin: two routes to growth hormone
Tesamorelin works through the GHRH receptor, the same receptor as the natural hormone it is modelled on. Ipamorelin, a five-amino-acid peptide, works through a different one: the receptor for growth hormone releasing peptides, the growth hormone secretagogue receptor, also called the ghrelin receptor. In early laboratory research it released growth hormone without raising ACTH or cortisol, a selectivity its authors compared to GHRH itself (Raun et al., 1998).
Two receptors, one output: that is the logic behind studying them together. Our Tesamorelin + Ipamorelin Stack pairs a Tesamorelin vial with an Ipamorelin vial. The liver trials above used tesamorelin on its own.
Studying tesamorelin
Every liver result in this article comes from tesamorelin, and our Tesamorelin is ready to order, on its own or in the stack. It arrives as a lyophilised powder and is reconstituted with bacteriostatic water; the tesamorelin reconstitution guide covers the arithmetic.
Tesamorelin is supplied for laboratory research use only. For more on this compound, see Tesamorelin and Visceral Fat: The Trial Record, Tesamorelin: One Small Change to a Natural Hormone and Weight Loss and Metabolism Research.
Frequently asked questions
Does tesamorelin reduce liver fat?
In a 2019 Lancet HIV trial of 61 people with HIV and fatty liver, liver fat fell 4.1 percentage points more on tesamorelin than on placebo over 12 months, a 37% relative reduction, and 35% against 4% finished the year below 5% liver fat. A 2014 JAMA trial of 50 people with HIV reported liver fat moving the same way over six months.
Did tesamorelin affect liver fibrosis?
On repeat biopsy in the 2019 trial, fibrosis progressed in 2 people on tesamorelin (10.5%) against 9 on placebo (37.5%), P=0.04. Fibrosis that was already present at the start did not improve compared with placebo.
Did people lose weight in the tesamorelin liver trial?
No. Body weight, BMI and waist size did not change over the 12 months, and diet and activity records were stable. Visceral fat fell and lean mass rose modestly while liver fat came down.
Why is tesamorelin paired with ipamorelin?
They raise growth hormone through different receptors: tesamorelin through the GHRH receptor and ipamorelin through the growth hormone secretagogue receptor, also called the ghrelin receptor. The Tesamorelin + Ipamorelin Stack supplies one vial of each.
Where can I buy tesamorelin in Canada?
Vistara Labs supplies Tesamorelin as a lyophilised vial, on its own or in the Tesamorelin + Ipamorelin Stack, shipped from within Canada to every province. Laboratory research use only.
Sources: 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. PMID 31611038. 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. PMID 25038357. Raun K et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998. PMID 9849822.
References
Tesamorelin has been studied in randomised placebo-controlled trials measuring body composition and liver fat directly.
- Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extensionRandomised placebo-controlled trial with safety extension; 404 people with HIV-associated abdominal fat accumulation.
- Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trialRandomised, double-blind, multicentre trial in people with HIV and non-alcoholic fatty liver disease, 12 months.
Links open the study record on PubMed so the source can be checked directly. Listing a study is not a claim that its findings apply to any other use, product or route of administration. Research use only.
