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

🥉 Top 5% JournalNov 18, 2025Liver international : official journal of the International Association for the Study of the Liver

GLP-1RA and Liver Scarring Progression in Fatty Liver Disease with Type 2 Diabetes Using Matched Patient Data

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Abstract

GLP-1 receptor agonist (GLP-1RA) use was associated with a lower risk of liver fibrosis progression in patients with type 2 diabetes and early-stage metabolic dysfunction-associated steatotic liver disease.

GLP-1RA users had an incidence rate of 3.25 per 100 person-years for fibrosis progression, compared to 4.29 for those using dipeptidyl peptidase-4 inhibitors (DPP-4i).
The hazard ratio for fibrosis progression in GLP-1RA users was 0.75, indicating a 25% reduction in risk compared to DPP-4i users.
Risk reduction with GLP-1RA was consistent across various subgroups, including those with low baseline fibrosis scores and lower body mass index.
No significant differences in secondary liver-related outcomes were observed between GLP-1RA and DPP-4i users.

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BACKGROUND AND AIMS: GLP-1 receptor agonists (GLP-1RA) are widely used in type 2 diabetes mellitus (T2DM) and may confer hepatoprotective effects in metabolic dysfunction-associated steatotic liver disease (MASLD). Their impact on liver fibrosis progression in real-world clinical settings remains unclear. This study evaluated the link between GLP-1RA use and liver fibrosis progression in T2DM patients with early-stage MASLD.

METHODS: We conducted a retrospective cohort study emulating a target trial using electronic health records from the Mass General Brigham (MGB) system between 2010 and 2023. Adults with MASLD and T2DM who initiated GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) therapy and had baseline Fibrosis-4 (FIB-4) scores < 2.67 were included. Propensity score matching (1:1) was applied to balance baseline covariates between groups. The primary outcome was progression to high-risk FIB-4 (> 2.67), confirmed by two consecutive values ≥ 90 days apart within a one-year period. The secondary outcome was a composite of cirrhosis, hepatic decompensation, hepatocellular carcinoma, or liver transplantation.

RESULTS: A total of 2238 matched pairs were analysed. GLP-1RA use was associated with a lower risk of fibrosis progression compared to DPP-4i (incidence rate 3.25 vs. 4.29 per 100 person-years; HR 0.75, 95% CI 0.65-0.87). Results were consistent in per-protocol (HR 0.80) and landmark sensitivity analyses. The risk reduction was also observed across subgroups, including those with low baseline FIB-4, BMI < 30, and users of statins, aspirin or metformin. No significant difference was found in secondary liver-related outcomes (HR 0.98, 95% CI 0.72-1.34).

CONCLUSION: GLP-1RA use significantly reduced the risk of liver fibrosis progression in patients with MASLD and T2DM, supporting its potential role in early disease modification.

Key numbers

0.75

Decrease in Risk

Hazard ratio for vs. users.

3.25 per 100 person-years

Incidence Rate of

Compared to 4.29 per 100 person-years for users.

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Abstract

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