Among adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH), treatment with glucagon-like peptide 1 receptor agonists (GLP-1RAs), particularly semaglutide or liraglutide, is associated with higher rates of MASH resolution without worsening of fibrosis, according to a recent Singapore study.
In this pooled analysis, patients treated with GLP-1RA were more likely to achieve histologic resolution of MASH without fibrosis progression, the primary endpoint of the study, than those treated with placebo (pooled risk ratio [RR], 2.04). This result indicated that GLP-1RA treatment more than doubled the likelihood of achieving this outcome.
Patients receiving GLP-1RA also demonstrated a ≥1-stage improvement in fibrosis without aggravating MASH activity, a secondary endpoint of the study, relative to those receiving placebo (pooled RR, 1.53). Of note, “this modest change is unsurprising given the relatively short treatment duration (48–72 weeks) and the typically gradual pace of fibrosis recovery,” said the researchers.
“Nevertheless, the direction effect suggests that GLP-1RAs may facilitate not only histologic remission but also structural hepatic improvement,” they noted.
With regard to safety, a slight increase in overall adverse events (AEs) was observed in the GLP-1RA group than in the placebo group (pooled RR, 1.08), though these AEs were considered mild to moderate in severity and did not lead to treatment discontinuation.
The most frequently reported AEs were gastrointestinal symptoms, such as nausea, vomiting, and diarrhoea, consistent with the established safety profile of GLP-1RAs, as noted by the researchers.
“The collective findings strengthen the case for semaglutide and liraglutide as promising therapeutic agents that address both metabolic and histologic aspects of MASH while preserving a favourable safety profile,” according to the researchers.
This recent systematic review and meta-analysis of three RCTs was conducted to assess the impact of GLP-1RAs on the histological resolution of MASH, improvement in liver fibrosis, and safety outcomes. A total of 1,172 adults with biopsy-confirmed MASH were randomized to receive either GLP-1RAs, specifically semaglutide or liraglutide (n=800; age 50–56.3 years) or placebo (n=372; age 52–55.4 years). [Proceedings of Singapore Healthcare 2026;doi:10.1177/20101058261424018]
“Given the combined metabolic and hepatic benefits of GLP-1RAs, they emerge as promising candidates for the management of MASH, particularly among individuals who also have obesity or T2D,” said the researchers.
“The current evidence reinforces their growing role in liver-targeted therapy and highlights their potential as disease-modifying treatments for MASH,” they added.
However, “larger and longer-duration randomized trials are essential to verify their effects on fibrosis regression and on clinically meaningful endpoints such as cirrhosis, hepatic decompensation, and liver-related mortality,” the researchers noted.