Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis
- Design
- Randomized trial · 800 participants · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationParticipants had biopsy-proven MASH with significant fibrosis; most had obesity and many had diabetes. Histologic endpoints, not clinical outcomes.
- Could weight loss explain it?
- PossiblyWeight loss (-10.5%) is itself an effective MASH treatment; the abstract does not separate drug and weight effects.
- Study tier
- Study tier 1Large phase 3 RCT meeting both histologic primary endpoints; clinical-outcome part still ongoing.
- Assessment
- Version 4 · Checked against the source by AI · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
In a planned interim analysis of the first 800 of 1,197 people with MASH and moderate-to-advanced liver fibrosis, 72 weeks of semaglutide resolved steatohepatitis in 63% vs 34% on placebo and improved fibrosis in 37% vs 22%, judged by liver biopsy. Bodily pain scores did not differ between the groups, and gastrointestinal side effects were more common with semaglutide. Strong evidence of improved liver biopsy results in this liver disease (an interim result of an ongoing trial); effects on clinical outcomes are not yet reported. Unknown whether it applies to lean MASH or to people without liver disease.
01Findings
What the study reported
- Drugs
- Semaglutide
- Dose
- 2.4 mg once weekly
- Route
- subcutaneous
- Treatment duration
- 72 weeks (interim of a 240-week trial)
- Comparator
- placebo
- Primary outcome
- Resolution of steatohepatitis without worsening fibrosis; reduction in fibrosis without worsening steatohepatitis (histology at 72 weeks)
- Effect
- 62.9% vs 34.3% (difference 28.7 pp); fibrosis 36.8% vs 22.4% (difference 14.4 pp); weight -10.5% vs -2.0%
- 95% confidence interval
- 21.1 to 36.2; 7.5 to 21.3
- P value
- <0.001
- Follow-up
- 72 weeks
- Adverse events
- GI adverse events more common with semaglutide.
- Limitations
- Not extracted
Who was studied
- Obesity status
- not required; majority had obesity (full text)
- Diabetes status
- mixed (about half with T2D, full text)
- Baseline condition
- biopsy-proven MASH with fibrosis stage 2-3
- Sample size
- 800
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 800
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo
- Follow up duration
- 72 weeks
- Outcome type
- histologic surrogate accepted by regulators
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 21.1 to 36.2; 7.5 to 21.3
- Risk of bias
- interim analysis of ongoing trial
- Funding conflicts
- yes
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Novo Nordisk
- Industry funded
- Yes
- Manufacturer
- Novo Nordisk
- Sponsor role
- Sponsor designed and analysed.
- Author conflicts
- Authors report Novo Nordisk relationships; sponsor co-authors.
- Independent replication
- no
- Notes
- Authors declare relationships with the drug's manufacturer: Novo Nordisk
Funding is shown on every study and never used to score it.
03Claims
Claims this study bears on
- Semaglutide improves liver histology in MASH with fibrosis.Supports
Phase 3 interim histology endpoints met; Novo Nordisk funded.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Semaglutide, a glucagon-like peptide-1 receptor agonist, is a candidate for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). [METHODS] In this ongoing phase 3, multicenter, randomized, double-blind, placebo-controlled trial, we assigned 1197 patients with biopsy-defined MASH and fibrosis stage 2 or 3 in a 2:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. The results of a planned interim analysis conducted at week 72 involving the first 800 patients are reported here (part 1). The primary end points for part 1 were the resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis. [RESULTS] Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% confidence interval [CI], 21.1 to 36.2; P<0.001). A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of the patients in the semaglutide group and in 22.4% of those in the placebo group (estimated difference, 14.4 percentage points; 95% CI, 7.5 to 21.3; P<0.001). Results for the three secondary outcomes that were included in the plan to adjust for multiple testing were as follows: combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% of the patients in the semaglutide group and in 16.1% of those in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2 to 22.8; P<0.001). The mean change in body weight was -10.5% with semaglutide and -2.0% with placebo (estimated difference, -8.5 percentage points; 95% CI, -9.6 to -7.4; P<0.001). Mean changes in bodily pain scores did not differ significantly between the two groups. Gastrointestinal adverse events were more common in the semaglutide group. [CONCLUSIONS] In patients with MASH and moderate or advanced liver fibrosis, once-weekly semaglutide at a dose of 2.4 mg improved liver histologic results. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT04822181.).
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 40305708 first ingestion |