A major update for liver disease care has emerged from recent clinical research showing that semaglutide can improve liver outcomes for people with metabolic dysfunction-associated steatohepatitis (MASH) even when weight loss is minimal. This could offer new hope for managing a serious condition that currently has limited drug treatments.
MASH is a progressive liver condition in which fat accumulation triggers inflammation and scarring (fibrosis). In time, it can lead to cirrhosis, liver failure or cancer. Until now, clinicians have relied mainly on lifestyle changes , such as diet and exercise , to slow disease progression.
A post hoc analysis of the phase III ESSENCE clinical trial revealed that adults with moderate-to-advanced MASH who received semaglutide 2.4 mg (brand name Wegovy®) weekly for 72 weeks experienced significant improvements in liver health compared with placebo.
Importantly, these improvements occurred even in patients with very low weight loss (≤2%), challenging the long-held assumption that semaglutide’s liver effects come mainly from weight reduction.
Key outcomes of the analysis show: In participants with minimal weight loss, 48.4 % of those on semaglutide achieved resolution of liver inflammation, compared with 25.8 % of those on placebo.
27.2 % of semaglutide patients showed improvements in liver scarring, while only 18.3 % of placebo participants did.
These figures suggest that semaglutide’s benefits may arise from direct effects on liver metabolism and inflammation, not just through weight loss.
The ESSENCE trial, which involved hundreds of participants across many countries, also found that semaglutide:
Reduced liver inflammation (steatohepatitis) and improved fibrosis markers more than placebo. Helped improve key liver enzymes and other markers of liver health.
Independent meta-analysis of randomized clinical trials supports this broader trend. These analyses show semaglutide lowers liver fat and fibrosis scores and improves enzyme levels in patients with or at risk of MASH.
Semaglutide belongs to a class of drugs known as GLP-1 receptor agonists. They improve blood sugar control and reduce appetite, helping many patients lose weight. But evidence now suggests this class may also exert direct beneficial effects on liver cells and metabolic pathways.
Experts argue that weight loss alone cannot fully explain the improvements in liver inflammation and fibrosis seen in the ESSENCE analysis. This indicates the drug may act directly on metabolic processes in liver tissue.
MASH affects tens of millions worldwide, including many , where non-alcoholic fatty liver disease is one of the fastest-growing causes of liver-related illness.
While semaglutide is already available for obesity and type 2 diabetes, it is not yet licensed specifically for MASH here. However, the new data may influence future treatment guidelines and regulatory decisions, expanding therapeutic options for liver disease beyond lifestyle approaches.
Clinicians will likely monitor ongoing research and regulatory updates closely. The next phase of the ESSENCE trial is expected to extend follow-up and deepen understanding of long-term effects.
Semaglutide’s safety profile remains mostly consistent with its known effects: gastrointestinal symptoms such as nausea, diarrhoea and constipation are among the most common side effects.
Patient communities and advocacy groups have welcomed the research. Many point out that until now, MASH treatment options have been limited to weight loss and managing metabolic risk factors. A drug that shows direct liver benefit regardless of weight loss could be a transformative tool.
Regulatory decisions , will determine whether semaglutide becomes an approved treatment option for MASH outside of its current uses. Clinicians and researchers are keen to see long-term outcomes on liver disease progression and related complications such as cirrhosis or liver cancer.
In the meantime, semaglutide’s reported liver benefits add to growing evidence that GLP-1 receptor agonists can play a broader role in metabolic and liver disease management, moving beyond weight control to address underlying pathology directly.
References
- Patient Care Online. (2026, January 15). Semaglutide May Improve Liver Outcomes, Regardless of Weight Loss Effects in MASH: Daily Dose. Retrieved from https://www.patientcareonline.com/view/semaglutide-may-improve-liver-outcomes-regardless-of-weight-loss-effects-in-mash-daily-dose
- ScienceDaily. (2025, May 4). Semaglutide treats liver disease in two thirds of patients. Retrieved from https://www.sciencedaily.com/releases/2025/04/250430182815.htm
- Pharmacally. (2025). Novo Nordisk’s Wegovy® (Semaglutide 2.4 mg) delivers liver health benefits beyond weight loss. Retrieved from https://pharmacally.com/novo-nordisks-wegovy-semaglutide-2-4-mg-delivers-liver-health-benefits-beyond-weight-loss-in-adults-with-mash-new-post-hoc-analysis-from-essence-trial/
- PR Newswire. (2025). Novo Nordisk’s Wegovy® (semaglutide 2.4 mg) was associated with liver health-related benefits. Retrieved from https://www.prnewswire.com/news-releases/novo-nordisks-wegovy-semaglutide-2-4-mg-was-associated-with-liver-health-related-benefits-not-solely-based-on-weight-loss-in-adult-patients-with-mash-with-liver-scarring-302610186.html
- PubMed. (2025). The impact of semaglutide on liver outcomes in patients with or at risk of MASH: A meta-analysis. Retrieved from https://pubmed.ncbi.nlm.nih.gov/41286982/
