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GLP-1RA and Liver Fibrosis Progression in MASLD and Type 2 Diabetes: Target Trial Emulation Using Propensity Score

Jonggi Choi1,2,3, Tushar Kamath3, Vy H Nguyen4

  • 1Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Liver International : Official Journal of the International Association for the Study of the Liver
|November 18, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RA) significantly slowed liver fibrosis progression in patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). This suggests GLP-1RA may be beneficial for early MASLD management.

Area of Science:

  • Hepatology
  • Endocrinology
  • Pharmacology

Background:

  • Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) often coexist.
  • Glucagon-like peptide-1 receptor agonists (GLP-1RA) are established T2DM treatments with potential liver benefits.
  • The effect of GLP-1RA on liver fibrosis progression in MASLD patients is not well-defined in real-world settings.

Purpose of the Study:

  • To investigate the association between GLP-1RA use and liver fibrosis progression in T2DM patients with early-stage MASLD.
  • To compare fibrosis progression rates between GLP-1RA users and dipeptidyl peptidase-4 inhibitor (DPP-4i) users.

Main Methods:

  • Retrospective cohort study emulating a target trial using electronic health records (2010-2023).
  • Included T2DM patients with MASLD and baseline Fibrosis-4 (FIB-4) score < 2.67, initiating GLP-1RA or DPP-4i.
  • Propensity score matching (1:1) was used; primary outcome was progression to high-risk FIB-4 (≥ 2.67).

Main Results:

  • 2238 matched pairs were analyzed.
  • GLP-1RA use was associated with a lower risk of fibrosis progression compared to DPP-4i (HR 0.75; 95% CI 0.65-0.87).
  • This risk reduction was consistent across subgroups and sensitivity analyses, with no significant difference in secondary liver outcomes.

Conclusions:

  • GLP-1RA significantly reduced liver fibrosis progression in T2DM patients with MASLD.
  • Findings support GLP-1RA's potential role in modifying early-stage MASLD.
  • Further research may elucidate specific mechanisms of hepatoprotection.
Keywords:
GLP‐1RAMASLDliver fibrosis

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