Evidence map›Paper›PMID 40268291›Full record

ArticleClinical and molecular hepatology2025

Glucagon-like peptide 1 receptor agonist and reduced liver and non-liver complications in adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease: a target trial emulation study.

Xianhua Mao, Xinrong Zhang, Rongtao Lai, Ka-Shing Cheung, Man-Fung Yuen, Ramsey Cheung, Wai-Kay Seto, Mindie H Nguyen

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In one paragraph

Article in Clinical and molecular hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Xianhua MaoDivision of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
Xinrong ZhangDivision of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
Rongtao LaiDivision of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
Ka-Shing CheungDepartment of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.
Man-Fung YuenDepartment of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.
Ramsey CheungDivision of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
Wai-Kay SetoDepartment of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong.
Mindie H NguyenDivision of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.

Funding

Stanford Center for Clinical & Translational Education and Research (Spectrum)UL1TR003142 · NCATS · STANFORD UNIVERSITY · PI O'HARA, RUTH M · 2019 to 2023
$45.0M
Internal StanfordNational Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award UL-1TR003142NCATS NIH HHS UL1 TR003142University of Hong Kong
6 · The paper itself

Abstract

BACKGROUND/

aimsInformation about the association of glucagon-like peptide-1 receptor (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes.

methodsPatients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative™ Marketscan® Research Databases. Primary outcomes included incidences of (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI).

resultsIn the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1,000 person-years) of HCC (0.8 vs. 1.7; HR 0.53, 95% CI 0.39-0.71), of cirrhosis (29.3 vs. 32.9; HR 0.91, 95% CI 0.86-0.96), of CVD (57.2 vs. 73.9; HR 0.90, 95% CI 0.86-0.95), of CKD (4.5 vs. 6.8; HR 0.73, 95% CI 0.64-0.84), and of non-liver cancer (16.9 vs. 22.9; HR 0.82, 95% CI 0.77-0.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60-0.77.

conclusionIn this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications.

Indexed as

Diabetes Mellitus, Type 2Fatty LiverGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsAdultAgedCarcinoma, HepatocellularCardiovascular DiseasesDipeptidyl-Peptidase IV InhibitorsFemaleGlucagon-Like Peptide-1 ReceptorHumansIncidenceLiver CirrhosisLiver NeoplasmsMaleDipeptidyl-Peptidase IV InhibitorsGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsCardiovascular diseaseFatty liverLiver cancerMetabolic dysfunction-associated steatotic liver diseaseNon-alcoholic fatty liver disease

Identifiers

PMID40268291
PMCPMC12260620

What Socratic holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.