Key Clinical Summary: 

• A national study of 21 860 veterans with metabolic dysfunction-associated steatotic liver disease (MASLD) found that semaglutide was associated with a 16% lower hazard of fibrosis progression compared with dipeptidyl peptidase-4 (DPP-4) inhibitors.
• Fibrosis progression occurred in 1715 participants, while 228 experienced major adverse liver outcomes, including hepatocellular carcinoma, hepatic decompensation, liver transplantation, or liver-related death.
• No statistically significant difference in major adverse liver outcomes was observed between treatment groups, highlighting the need for longer-term studies.

Semaglutide was associated with a significantly lower risk of liver fibrosis progression compared with DPP-4 inhibitors among patients with MASLD without advanced fibrosis at baseline, according to research presented at the American Association for the Study of Liver Diseases (AASLD) meeting.

The findings, presented in abstract 0070, suggest that semaglutide may provide benefits across a broader population with MASLD beyond patients with metabolic dysfunction-associated steatohepatitis (MASH) and stage 2 or 3 fibrosis.

National Veterans Cohort Evaluates Fibrosis Progression

Researchers conducted a target trial emulation using Veterans Health Administration data collected between September 2017 and October 2025.

The study included 21 860 adults with MASLD who initiated either semaglutide (n = 14,182) or a DPP-4 inhibitor (n = 7678).

Participants had evidence of hepatic steatosis on imaging, at least 1 cardiometabolic risk factor, no harmful alcohol use, and a baseline Fibrosis-4 (FIB-4) index below 2.67.

The median age was 64.2 years, and 86.1% of participants were male.

Investigators used inverse probability of treatment weighting to balance baseline characteristics between treatment groups.

The primary outcome was progression to high fibrosis risk, defined as a FIB-4 score exceeding 2.67, confirmed by 2 measurements obtained 3 to 12 months apart.

Semaglutide Associated With 16% Lower Fibrosis Progression Hazard

Fibrosis progression was identified in 1715 participants, representing 7.0% of the study population as reported in the abstract.

Compared with DPP-4 inhibitors, semaglutide was associated with a 16% lower adjusted hazard of fibrosis progression (adjusted hazard ratio, 0.84; 95% CI, 0.78-0.90; P < .0001).

Median treatment duration was 1.2 years for semaglutide and 1.1 years for DPP-4 inhibitors.

However, no statistically significant difference was observed in major adverse liver outcomes, which occurred in 228 participants (1.0%).

The researchers suggested that the relatively short follow-up period and low frequency of liver-related events may have limited the ability to detect differences between treatments.

Importantly, progression was assessed using FIB-4, a noninvasive fibrosis risk index, rather than biopsy-confirmed changes in liver fibrosis.

Implications for Managed Care

The findings provide real-world evidence relevant to managed care organizations evaluating treatment strategies for patients with MASLD and cardiometabolic comorbidities.

A potential reduction in fibrosis progression could have implications for long-term disease management and prevention of advanced liver complications.

However, the study did not establish whether semaglutide reduces liver-related hospitalizations, mortality, or health care expenditures.

Additionally, the observational design limits causal interpretation, and the predominantly male veteran population may limit generalizability to other insured populations.

Conclusion

This national Veterans Health Administration analysis found that semaglutide was associated with a 16% lower hazard of FIB-4-defined fibrosis progression compared with DPP-4 inhibitors among patients with MASLD without advanced fibrosis at baseline.

Longer-term studies are needed to determine whether these findings translate into fewer serious liver-related complications and improved clinical outcomes.

Reference 

John B, Soon S, Dahman B, et al. Semaglutide and fibrosis progression: comparison with DPP-4 inhibitors. Abstract presented at: AASLD The Liver Meeting 2026; November 5-9, 2026; Denver, CO.