TY  - JOUR
T1  - Comparative Efficacy of Promising Targets in the Treatment of Metabolic Dysfunction-associated Steatotic Liver Disease and Steatohepatitis: A Systematic Review and Network Meta-analysis 
AU  - Ni, Wenjing
AU  - Li, Jie
AU  - Bai, Xue
AU  - Zhou, Sisi
AU  - Wu, Xiangyu
AU  - Jia, Leyao
AU  - Jiang, Zhuoru
AU  - Wu, Jiali
AU  - Li, Ming
AU  - Wong, Connie
AU  - Wu, Chao
AU  - Shi, Junping
AU  - Nguyen, Mindie H.
JF  - Journal of Clinical and Translational Hepatology
VL  - 
IS  - 000
SN  - 2310-8819
SP  - 
EP  - 
Y1  - 2026-07-20
DO  - 10.14218/JCTH.2025.00596
UR  - https://www.xiahepublishing.com/2310-8819/JCTH-2025-00596
AB  - Background and Aims 
Randomized controlled trials (RCTs) have been conducted to evaluate treatment efficacy for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis. This study aimed to compare the effectiveness and safety of 11 promising targets among adults with MASLD.
Methods
PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, Scopus, and Embase were searched from inception to November 20, 2024. The primary outcomes were fibrosis improvement ≥1 stage without worsening of steatohepatitis and steatohepatitis resolution without worsening of fibrosis. Additional outcomes included reductions in liver fat content, liver enzymes, metabolic profiles, and selected safety outcomes. The surface under the cumulative ranking curve (SUCRA) was used to rank efficacy.
Results
Of 11,584 articles screened, 44 eligible RCTs (11,410 participants, 33 medications) were included. For fibrosis improvement, d-(R)-pioglitazone (SUCRA: 79.3) and fibroblast growth factor (FGF) 21 analogs (SUCRA: 71.9) ranked higher. For steatohepatitis resolution, glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) dual receptor agonists (RAs) (SUCRA: 91.7) ranked higher. Co-agonists of GLP-1/GIP/GCG and GLP-1/GCG receptors ranked higher for relative and absolute changes in liver fat content, respectively. For liver enzymes and glucose improvement, the combination of a GLP-1 RA and an acetyl-coenzyme A carboxylase inhibitor ranked higher. GLP-1 RAs, peroxisome proliferator-activated RAs, and FGF21 analogs showed favorable effects on lipid profile improvement.
Conclusions
Incretin-based co-agonists and FGF21 analogs showed favorable profiles across key endpoints, while d-(R)-pioglitazone and GLP-1/GIP dual RAs ranked higher for fibrosis improvement and steatohepatitis resolution, respectively. SUCRA rankings should be interpreted in conjunction with effect sizes, uncertainty, and available safety data.