The main finding
In one sentence: Among 98 adults with fatty liver disease who took part in the retatrutide phase 2 trial, liver fat measured by MRI fell by 42.9% to 82.4% at 24 weeks depending on the dose, compared with a 0.3% rise with placebo.
Group averages, not an individual prediction. A trial result describes what happened to a defined group over a defined time.
On this page
Why this study matters
Retatrutide is an experimental medicine. It is not approved in Canada as of September 2026, and this study is research only. Fatty liver disease linked to metabolism, now called MASLD (metabolic dysfunction-associated steatotic liver disease), is common in people living with obesity. It can progress to inflammation and scarring. This substudy asked whether retatrutide, which acts on GIP, GLP-1 and glucagon receptors, reduces the amount of fat in the liver. It is a planned add-on to the main phase 2 obesity trial, which reported average weight reductions of 22.8% and 24.2% at 8 mg and 12 mg over 48 weeks.
Who was in the study
The substudy included 98 of the 338 people in the parent trial. All had obesity or overweight, did not have type 2 diabetes, and had MASLD with liver fat of at least 10% measured by MRI. The study ran for 48 weeks, with the main liver-fat measurement at 24 weeks. The published summary we reviewed does not report the age range or the countries where the trial was run.
What the researchers did
This was a prespecified substudy of a randomized, double-blind, placebo-controlled trial. Prespecified means the liver-fat question was planned before the trial started, not added later. Randomized means people were assigned to groups by chance. Double-blind means neither participants nor staff knew who was on the medicine. A placebo is an inactive injection.
Participants received once-weekly injections of retatrutide at 1, 4, 8 or 12 mg, or placebo, for 48 weeks. The primary objective was the mean relative change in liver fat from baseline to week 24, measured by MRI-PDFF. That is a type of MRI scan that estimates what percentage of the liver is fat. "Relative change" means the change as a percentage of the starting amount, so a person going from 20% liver fat to 10% would have a relative change of -50%.
The extracted data note that the efficacy analysis used an estimand that excludes data collected after events such as stopping treatment. An estimand is the precise question a trial's statistics are set up to answer. This one describes the effect while people stayed on the assigned treatment, rather than the effect regardless of what happened later.
What they found
At 24 weeks, the average relative change in liver fat was -42.9% with 1 mg, -57.0% with 4 mg, -81.4% with 8 mg and -82.4% with 12 mg, compared with +0.3% with placebo. All four retatrutide doses differed from placebo with P below 0.001 (R32-C74).
| Group | Relative change in liver fat at 24 weeks | Reached normal liver fat (under 5%) at 24 weeks |
|---|---|---|
| Retatrutide 1 mg | -42.9% | 27% |
| Retatrutide 4 mg | -57.0% | 52% |
| Retatrutide 8 mg | -81.4% | 79% |
| Retatrutide 12 mg | -82.4% | 86% |
| Placebo | +0.3% | 0% |
The authors report that the reductions in liver fat were significantly related to changes in body weight, abdominal fat, and measures linked to insulin sensitivity and lipid metabolism. The published summary we reviewed does not give between-group differences with confidence intervals.
Side effects and people who stopped
The published summary we reviewed does not report side effects or the number of people who stopped treatment in this substudy. The extracted data note that a week 48 MRI scan was available for 43.9% of participants, which means the later time point rests on fewer than half of the people enrolled. For the side-effect profile of retatrutide in the parent trial, see the page on the phase 2 obesity trial linked below.
What this study does not tell you
- It is a small, selected substudy of 98 people chosen because they had a high amount of liver fat on MRI. It is not a trial designed around liver disease from the start.
- Liver fat on MRI is not the same as a biopsy. The study did not measure inflammation (MASH) or fibrosis, which are what cause harm over time.
- Week 48 scans were available for 43.9% of participants, so the longer-term picture is incomplete.
- The main analysis describes the effect while people stayed on treatment. It does not describe what happens to liver fat if the medicine is stopped.
- People with type 2 diabetes were excluded, so the results do not apply to them.
- Retatrutide is not approved in Canada as of September 2026.
- The extracted data note that the funder was involved in the design, data collection, analysis, interpretation and writing of the study.
- Do not compare these figures with liver results from trials of other medicines. Different trials use different measures and enrol different people.
What it means in Canada
Retatrutide is not approved in Canada as of September 2026, and this substudy is part of the evidence for a medicine still in development. You can follow emerging medicines on our medicines page. For medicines available in Canada, see semaglutide in Canada and tirzepatide in Canada, and public drug coverage by province.
Common questions
How much did retatrutide reduce liver fat?
At 24 weeks, the relative change in liver fat was -42.9% at 1 mg, -57.0% at 4 mg, -81.4% at 8 mg and -82.4% at 12 mg, compared with +0.3% with placebo.
How many people reached a normal amount of liver fat on retatrutide?
At 24 weeks, liver fat below 5% was reached by 27% at 1 mg, 52% at 4 mg, 79% at 8 mg and 86% at 12 mg, and by 0% of the placebo group.
Does this study show retatrutide treats liver scarring?
No. It measured liver fat by MRI. It did not measure inflammation or fibrosis with a biopsy, and retatrutide is not approved in Canada as of September 2026.
Related reading
Other studies in this library that bear on the same question.
Retatrutide phase 2: weight change over 48 weeks
ESSENCE: semaglutide for MASH liver disease
Semaglutide phase 2 NASH trial, 2021
TRANSCEND-T2D-1: retatrutide in type 2 diabetes
Source
Original paper: Arun J Sanyal, Emerging evidence: retatrutide MASLD substudy of NCT04881760, Nature medicine, 2024. PubMed: https://pubmed.ncbi.nlm.nih.gov/38858523/. DOI: https://doi.org/10.1038/s41591-024-03018-2. Funding: The summary we reviewed does not state the funding source, although the extracted data record that the funder was involved in the design, analysis and writing of the study. How we summarized it: full text and extracted data.
This page explains a published study. It is not medical advice and does not describe whether a medicine is right for you. Talk to your doctor, nurse practitioner or pharmacist about your own situation. Reviewed and signed by two pharmacists registered in British Columbia, 2026-09-18.
Evidence records behind this page
Each record is a row in the clinical evidence file, taken from the published paper named above. The caution column is the limit the researcher recorded for that number.
This table scrolls sideways.
| Record | What the paper reports | Type | Population | Caution | Source |
|---|---|---|---|---|---|
| R32-C74 | In the 98-person retatrutide MASLD substudy, relative liver-fat changes at 24 weeks were -42.9%, -57.0%, -81.4% and -82.4% with 1, 4, 8 and 12 mg, versus +0.3% with placebo; liver fat was measured by MRI. | direct evidence | Adults with obesity/overweight without T2D and MASLD with liver fat at least 10% by MRI | Small selected MRI substudy; liver fat is not a biopsy-confirmed MASH or fibrosis outcome. Week 48 MRI available for 43.9%. Canadian authorization status not verified; linked disclosures/supplements not extracted. | PubMed 38858523 |