Retatrutide reduced the amount of fat in the liver by 86.0 percent over 48 weeks at a dose of 12 mg. This was the result of a phase two trial published in 2024 in Nature Medicine. After 48 weeks, 93 percent of people in that group had a liver free of fatty disease. If you want to know how retatrutide acts on the liver and how it compares with other peptides, below you will find all the figures from that trial.
What is metabolic fatty liver disease?
It is a condition in which excess fat builds up in liver cells because of metabolic disorders. Its current name is MASLD, short for metabolic dysfunction-associated steatotic liver disease. The same condition used to be called non-alcoholic fatty liver disease, or NAFLD. The retatrutide trial was run in people with obesity or overweight.
The amount of fat in the liver is now measured by magnetic resonance imaging using the MRI-PDFF method. The result is given as the percentage of fat in liver tissue. The authors of the retatrutide trial counted a result below 5 percent as normal. The trial enrolled people whose liver was at least 10 percent fat.
How was the retatrutide liver trial run?
The trial was part of a larger, 48-week phase two trial in obesity. It included 98 people with fatty liver, without type 2 diabetes. The average age was 46.6, the average BMI 38.4, and women made up 46.9 percent of the group. Participants were randomly assigned to doses of 1, 4, 8 or 12 mg or to placebo.
Retatrutide was given under the skin once a week. Neither the participants nor the researchers knew who received the drug and who received placebo. The main outcome was the relative change in liver fat after 24 weeks. The measurement was repeated after 48 weeks.
How much did liver fat fall after 24 weeks?
After 24 weeks liver fat fell by 81.4 percent at 8 mg and by 82.4 percent at 12 mg. In the placebo group it hardly changed. The differences from placebo were statistically significant at every retatrutide dose. The result clearly depended on the dose.
| Dose | Change in liver fat after 24 weeks | Liver free of fatty disease after 24 weeks | Liver fat down by at least 30 percent |
|---|---|---|---|
| 1 mg | -42.9 percent | 27 percent of people | 71 percent of people |
| 4 mg | -57.0 percent | 52 percent of people | 89 percent of people |
| 8 mg | -81.4 percent | 79 percent of people | 100 percent of people |
| 12 mg | -82.4 percent | 86 percent of people | 100 percent of people |
| placebo | +0.3 percent | 0 percent of people | 4 percent of people |
After less than six months, most people on the higher doses already had a normal liver. At 8 and 12 mg, every participant reached a fall in liver fat of at least 30 percent.
What did the full 48 weeks show?
After 48 weeks liver fat fell by 86.0 percent at 12 mg and by 81.7 percent at 8 mg. At 1 mg the fall was 51.3 percent, and at 4 mg 59.0 percent. In the placebo group liver fat fell by 4.6 percent. A liver free of fatty disease was seen in 93 percent of people at 12 mg and 89 percent at 8 mg.
Over the same time participants lost a lot of body weight. The loss was 8.6 percent at 1 mg, 16.3 percent at 4 mg, 23.8 percent at 8 mg and 25.9 percent at 12 mg. In the placebo group body weight hardly changed. The authors showed that the fall in liver fat was linked to the fall in body weight and abdominal fat.
What did the main trial behind this group show?
The main trial included 338 adults with obesity, or overweight with a related condition. It was published in 2023 in the New England Journal of Medicine. Men made up 51.8 percent of the participants. Retatrutide was given once a week for 48 weeks, at doses from 1 to 12 mg.
| Dose | Weight loss after 24 weeks | Weight loss after 48 weeks |
|---|---|---|
| 1 mg | 7.2 percent | 8.7 percent |
| 4 mg | 12.9 percent | 17.1 percent |
| 8 mg | 17.3 percent | 22.8 percent |
| 12 mg | 17.5 percent | 24.2 percent |
| placebo | 1.6 percent | 2.1 percent |
After 48 weeks, at least 15 percent of body weight was lost by 83 percent of people at 12 mg, 75 percent at 8 mg and 60 percent at 4 mg. In the placebo group 2 percent of participants reached that result.
The most common side effects were gastrointestinal and increased with the dose. A lower starting dose, 2 mg instead of 4 mg, eased them. Heart rate rose depending on the dose, peaking at week 24 and then falling. Phase three results from the TRIUMPH trials are in the guide on retatrutide phase 3.
Why does retatrutide act on the liver so strongly?
Retatrutide stimulates three receptors at once: GLP-1, GIP and glucagon. Semaglutide acts only on the first of them, and tirzepatide on the first two. The third, the glucagon receptor, sets retatrutide apart from both of those peptides. According to the trial authors, glucagon may reduce liver fat by stimulating fat burning in liver cells.
One of the blood measurements points in this direction. The concentration of beta-hydroxybutyrate, a marker of fatty acid burning, rose two- to threefold, depending on the dose. At higher doses adiponectin also rose, which the authors link to the loss of fat tissue. A comparison of three peptides for body weight is in the guide semaglutide vs tirzepatide vs retatrutide.
How does retatrutide compare with semaglutide and tirzepatide?
In the studies described by the authors, retatrutide gave the largest fall in liver fat. The authors themselves set it against earlier results for other peptides. Dulaglutide reduced liver fat by 32 percent after 24 weeks, and tirzepatide by 47 percent after 52 weeks. Semaglutide gave about 50 percent after 72 weeks.
| Peptide | Fall in liver fat | Time |
|---|---|---|
| Dulaglutide | 32 percent | 24 weeks |
| Tirzepatide | 47 percent | 52 weeks |
| Semaglutide | about 50 percent | 72 weeks |
| Retatrutide 12 mg | 82.4 percent | 24 weeks |
| Retatrutide 12 mg | 86.0 percent | 48 weeks |
These figures come from different trials and different groups of people, so they are not a direct comparison. They do show, however, that the advantage of retatrutide is clear. The effects of semaglutide and tirzepatide on the liver are described in the guide on semaglutide and tirzepatide for the heart, kidneys, sleep and liver.
What did blood tests and safety show?
The authors found no signals of liver damage. The liver enzymes ALT and AST were normal in participants from the start. That is why the absence of a clear change after treatment did not surprise the researchers. The most common side effects were gastrointestinal, transient and usually mild or moderate.
The fall in liver fat went hand in hand with better metabolic markers. The authors link it to improved insulin sensitivity and changes in fat metabolism. The trial included 98 people, so its results concern a relatively small group.
Where to buy retatrutide and how much does it cost?
In the shop, retatrutide comes in three versions from three manufacturers. Retatrutide 20 mg Bio-Peptide costs 200 EUR and is in stock. Retatrutide 20 mg Genheal costs 200 EUR on backorder. Retatrutide 40 mg Nouveaux in a pen costs 350 EUR, so 8.75 EUR per milligram instead of 10 EUR.
How many weeks a vial lasts at successive doses is calculated in the guide on how long a GLP-1 vial lasts. All versions are on the retatrutide page. Retatrutide is not a registered medicine, and in the shop it is material for laboratory research.
Frequently asked questions
Does retatrutide reduce fatty liver?
Yes. In a 2024 trial, liver fat fell after 48 weeks by 86.0 percent at 12 mg and by 81.7 percent at 8 mg.
How quickly does retatrutide act on the liver?
After 24 weeks liver fat fell by 82.4 percent at 12 mg. At that point 86 percent of people in that group had a liver free of fatty disease.
How many people got rid of fatty liver on retatrutide?
After 48 weeks, 93 percent of people at 12 mg and 89 percent at 8 mg had liver fat below 5 percent. In the placebo group nobody did.
Does retatrutide act on the liver more strongly than semaglutide?
According to the trial authors, semaglutide reduced liver fat by about 50 percent after 72 weeks. Retatrutide 12 mg gave 82.4 percent after only 24 weeks.
Why does retatrutide burn fat in the liver?
It stimulates the glucagon receptor, which according to the authors increases fatty acid burning in the liver. The marker of this burning, beta-hydroxybutyrate, rose two- to threefold.
Sources
- Sanyal AJ, Kaplan LM, Frias JP et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine, 2024, 30(7): 2037-2048. https://doi.org/10.1038/s41591-024-03018-2
- Jastreboff AM, Kaplan LM, Frías JP et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. New England Journal of Medicine, 2023, 389(6): 514-526. https://pubmed.ncbi.nlm.nih.gov/37366315/