Semaglutide and tirzepatide remove fat from the liver and reverse its inflammation. In the ESSENCE trial, inflammation of the fatty liver resolved in 62.9 percent of people on semaglutide and 34.3 percent on placebo. In the SYNERGY-NASH trial, tirzepatide at 15 mg resolved it in 62 percent of people and placebo in 10 percent. On magnetic resonance imaging tirzepatide cut the amount of fat in the liver roughly in half within a year. If you have a fatty liver and excess weight, below are the numbers from six trials of both molecules.
What is fatty liver disease?
Fatty liver disease is the build-up of fat in liver cells, most often with excess weight and metabolic disorders. Today it is called MASLD, metabolic dysfunction-associated steatotic liver disease. When the fat causes inflammation, the disease moves on to the form called MASH.
Over time MASH leads to fibrosis, the replacement of healthy tissue by scar tissue. Drug trials usually include people with fibrosis of stage F2 or F3, that is moderate or advanced. Liver fat is measured with magnetic resonance imaging, and inflammation and fibrosis are assessed in a liver biopsy.
How much liver fat does tirzepatide remove?
Tirzepatide reduced liver fat content from 15.71 percent by 8.09 percentage points within a year. That is roughly half of the fat in the liver at the start. The result comes from the SURPASS-3 MRI trial, published in 2022 in The Lancet Diabetes and Endocrinology.
- Participants: 296 people with type 2 diabetes, excess weight and a high fatty liver index.
- Comparison: tirzepatide 5, 10 or 15 mg once a week against daily insulin degludec.
- Result after 52 weeks: minus 8.09 percentage points on tirzepatide 10 and 15 mg against minus 3.38 on insulin.
- Belly fat: visceral and subcutaneous fat in the abdomen also fell.
People with the most liver fat at the start lost the most. The fall was also larger in people whose belly fat and body weight fell more.
How much liver fat does semaglutide remove?
Semaglutide reduced liver fat clearly more than placebo in two imaging trials. The first, from 2021, included 67 people with liver fat of at least 10 percent. After 48 weeks the amount of fat relative to the start was 53 percent lower on semaglutide than on placebo.
In the same trial more people on semaglutide lost at least 30 percent of their liver fat. This was so at weeks 24, 48 and 72. Liver enzymes, body weight and blood sugar also fell.
The second trial, SAMARA, came out in January 2026 and included 55 people. Participants received semaglutide 2.4 mg a week or placebo for 52 weeks.
| Result in the SAMARA trial after 52 weeks | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Liver fat down by at least 30 percent | 60 percent of people | 17 percent of people |
| Loss of at least 5 percent of body weight | 64 percent of people | 8.3 percent of people |
| Liver enzymes ALT, AST and GGT | fall significantly larger than on placebo | reference |
The SAMARA authors showed that the effect of treatment can be followed with simple blood tests and imaging, without another biopsy.
What did the ESSENCE trial of semaglutide show?
ESSENCE showed that semaglutide reverses liver inflammation and reduces its fibrosis. It is a phase 3 trial in 1,197 people with MASH and fibrosis of stage F2 or F3. The first results cover 800 people after 72 weeks, and the whole trial will last 240 weeks.
| Result after 72 weeks | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Resolution of inflammation without worsening of fibrosis | 62.9 percent | 34.3 percent |
| Reduction of fibrosis without worsening of inflammation | 36.8 percent | 22.4 percent |
| Both at once | 32.7 percent | 16.1 percent |
| Change in body weight | minus 10.5 percent | minus 2.0 percent |
The results were published in the New England Journal of Medicine in 2025. An earlier phase 2 trial from 2021 gave a similar result for inflammation, 59 against 17 percent at a daily dose of 0.4 mg. The difference in fibrosis was not yet significant there, and it was confirmed only by the larger ESSENCE.
What did the SYNERGY-NASH trial of tirzepatide show?
SYNERGY-NASH showed that tirzepatide reverses liver inflammation in more than half of people at the 10 and 15 mg doses. It included 190 people with MASH and fibrosis of stage F2 or F3. Participants received tirzepatide or placebo once a week for 52 weeks.
| Dose | Resolution of inflammation without worsening of fibrosis | Reduction of fibrosis by at least one stage |
|---|---|---|
| Placebo | 10 percent | 30 percent |
| Tirzepatide 5 mg | 44 percent | 55 percent |
| Tirzepatide 10 mg | 56 percent | 51 percent |
| Tirzepatide 15 mg | 62 percent | 51 percent |
The results were published in the New England Journal of Medicine in 2024. The most common adverse effects concerned the stomach and gut and were usually mild or moderate. This is a phase 2 trial, so tirzepatide still awaits a large phase 3 trial for this indication.
Semaglutide or tirzepatide for fatty liver?
Both work, and the choice depends on whether the strength of the effect or the amount of evidence matters more. There is no head-to-head comparison of the two molecules in liver disease. The table sets out their results from separate trials.
| Feature | Semaglutide | Tirzepatide |
|---|---|---|
| Key trial | ESSENCE, phase 3, 1,197 people | SYNERGY-NASH, phase 2, 190 people |
| Resolution of inflammation | 62.9 against 34.3 percent after 72 weeks | up to 62 against 10 percent after 52 weeks |
| Liver fat on imaging | a fall of at least 30 percent in 60 percent of people | a fall from 15.71 by 8.09 percentage points |
| Weekly dose in trials | 2.4 mg | 5, 10 or 15 mg |
Semaglutide has a phase 3 trial, the strongest data. A comparison of the two molecules for weight is shown in the guide semaglutide, tirzepatide or retatrutide. Retatrutide has its own liver results, described in the guide on retatrutide and fatty liver.
Glutathione, an antioxidant made in our cells, has also been studied for the liver. What these studies measured is described in the guide on glutathione and the liver. The other benefits of both molecules beyond weight are collected in the guide semaglutide and tirzepatide beyond weight loss.
Where to buy semaglutide and tirzepatide?
The shop has semaglutide 3 mg Bio-Peptide for 90 EUR, in stock. Tirzepatide comes in three versions: 20 mg Bio-Peptide for 200 EUR in stock, 20 mg Genheal for 200 EUR to order and 40 mg Nouveaux in a pen for 350 EUR in stock.
All brands are collected on the compound pages: semaglutide and tirzepatide. The products in the shop are material for laboratory research, not the medicines Wegovy or Mounjaro. Treatment of liver disease is a matter for a doctor.
Frequently asked questions
Does semaglutide treat fatty liver disease?
In the ESSENCE trial inflammation of the fatty liver resolved in 62.9 percent of people on semaglutide 2.4 mg and 34.3 percent on placebo after 72 weeks. Fibrosis decreased in 36.8 against 22.4 percent.
Does tirzepatide work on the liver?
Yes. In the SYNERGY-NASH trial liver inflammation resolved in 44 to 62 percent of people on tirzepatide and 10 percent on placebo after 52 weeks.
How much does tirzepatide reduce liver fat?
In the SURPASS-3 MRI trial liver fat content fell from 15.71 percent by 8.09 percentage points within a year, roughly by half.
Which drug works better on the liver?
There is no head-to-head comparison. Semaglutide has a phase 3 trial, and tirzepatide gave a similar rate of resolved inflammation in a phase 2 trial.
How can you check whether the liver is improving?
The SAMARA trial showed that the effect can be followed with the liver enzymes ALT and AST and with imaging, without another biopsy.
Sources
- Sanyal AJ, Newsome PN, Kliers I et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. New England Journal of Medicine, 2025, 392(21): 2089-2099. https://doi.org/10.1056/NEJMoa2413258
- Loomba R, Hartman ML, Lawitz EJ et al. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. New England Journal of Medicine, 2024, 391(4): 299-310. https://doi.org/10.1056/NEJMoa2401943
- Gastaldelli A, Cusi K, Fernández Landó L et al. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI). The Lancet Diabetes and Endocrinology, 2022, 10(6): 393-406. https://doi.org/10.1016/S2213-8587(22)00070-5
- Flint A, Andersen G, Hockings P et al. Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging. Alimentary Pharmacology and Therapeutics, 2021, 54(9): 1150-1161. https://doi.org/10.1111/apt.16608
- Ajmera V, Vuppalanchi R, Khalili M et al. Clinical Trial: Semaglutide Versus Placebo in NIT-Assessed MASH (SAMARA). Alimentary Pharmacology and Therapeutics, 2026, 63(8): 1080-1088. https://doi.org/10.1111/apt.70516
- Newsome PN, Buchholtz K, Cusi K et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. New England Journal of Medicine, 2021, 384(12): 1113-1124. https://doi.org/10.1056/NEJMoa2028395