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 2 · curated · Sep 13, 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 people with MASH and moderate-to-advanced liver fibrosis, 72 weeks of semaglutide resolved steatohepatitis in 63% vs 34% and improved fibrosis in 37% vs 22%. Strong evidence for this liver disease; 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
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
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
- 1197
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 1197
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo
- Follow up duration
- 240 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: 95% confidence interval [CI], 21
- 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 |