Pegozafermin and survodutide top the rankings for MASH treatment in network meta-analysis of 9,324 patients
In a NMA of 29 RCTs (9,324 patients), pegozafermin ranked highest for fibrosis regression (SUCRA 79.92) and MASH resolution (SUCRA 91.75), with survodutide (SUCRA 90.87) and tirzepatide (SUCRA 84.70) close behind for resolution.
Quick Facts
What This Study Found
Fibrosis regression top SUCRA: pegozafermin (79.92), cilofexor+firsocostat (71.38). MASH resolution top SUCRA: pegozafermin (91.75), survodutide (90.87), tirzepatide (84.70). 8 agents better than placebo for fibrosis; 12 for resolution. 29 RCTs, 9,324 patients.
Key Numbers
How They Did This
Network meta-analysis of PubMed/Embase (Jan 2020-Dec 2024). 29 RCTs, 9,324 patients with biopsy-proven MASH. SUCRA ranking for co-primary endpoints.
Why This Research Matters
With multiple MASH drugs in development, clinicians and trialists need to know which are most effective. This ranking shows peptide-based drugs (tirzepatide, semaglutide, survodutide, liraglutide) among the top performers.
The Bigger Picture
The MASH treatment landscape is rapidly evolving with multiple drug classes. GLP-1-based drugs (tirzepatide, semaglutide, survodutide) are among the most effective, alongside FGF21 analogues (pegozafermin) and thyroid hormone receptor agonists (resmetirom).
What This Study Doesn't Tell Us
NMA relies on indirect comparisons. Different trial durations and populations. Biopsy endpoints are imperfect. Not all agents have phase 3 data.
Questions This Raises
- ?Will pegozafermin's ranking hold in phase 3 trials?
- ?Is combination therapy (GLP-1 + FGF21) the future of MASH treatment?
- ?Should SUCRA rankings influence MASH prescribing guidelines?
Trust & Context
- Key Stat:
- Pegozafermin #1, peptide drugs prominent GLP-1-based drugs (tirzepatide, semaglutide, survodutide) rank among the most effective MASH treatments alongside FGF21 analogues in 29-trial NMA
- Evidence Grade:
- Network meta-analysis of 29 RCTs with SUCRA ranking. Comprehensive but relies on indirect comparisons.
- Study Age:
- Published in 2025; literature through December 2024.
- Original Title:
- Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis.
- Published In:
- Hepatology (Baltimore, Md.), 82(6), 1523-1533 (2025)
- Authors:
- Souza, Matheus(2), Al-Sharif, Lubna(2), Antunes, Vanio L J(2), Huang, Daniel Q, Loomba, Rohit
- Database ID:
- RPEP-13660
Evidence Hierarchy
Frequently Asked Questions
Which drug is best for fatty liver disease (MASH)?
This analysis of 29 clinical trials ranked pegozafermin (an FGF21 analogue) highest for both reducing liver scarring and resolving fatty liver inflammation. Survodutide and tirzepatide—GLP-1-based drugs—ranked #2 and #3 for disease resolution. Multiple drugs showed significant benefits over placebo.
Are GLP-1 drugs effective for liver disease?
Yes. Tirzepatide, semaglutide, survodutide, and liraglutide all ranked among the effective treatments for MASH resolution. These drugs improve liver disease through weight loss, reduced inflammation, and metabolic improvement, making them strong options for patients with both obesity and fatty liver disease.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-13660APA
Souza, Matheus; Al-Sharif, Lubna; Antunes, Vanio L J; Huang, Daniel Q; Loomba, Rohit. (2025). Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis.. Hepatology (Baltimore, Md.), 82(6), 1523-1533. https://doi.org/10.1097/HEP.0000000000001254
MLA
Souza, Matheus, et al. "Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis.." Hepatology (Baltimore, 2025. https://doi.org/10.1097/HEP.0000000000001254
RethinkPeptides
RethinkPeptides Research Database. "Comparison of pharmacological therapies in metabolic dysfunc..." RPEP-13660. Retrieved from https://rethinkpeptides.com/research/souza-2025-comparison-of-pharmacological-therapies
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.