Pegozafermin and survodutide top the rankings for MASH treatment in network meta-analysis of 9,324 patients | Research

The takeaway

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.

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

What the researchers 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.

Why it 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.

How the study worked

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.

What this study cannot tell us

NMA relies on indirect comparisons. Different trial durations and populations. Biopsy endpoints are imperfect. Not all agents have phase 3 data.

How to read the evidence

Network meta-analysis of 29 RCTs with SUCRA ranking. Comprehensive but relies on indirect comparisons.

When this study was published

Published in 2025; literature through December 2024.

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).

Questions still open

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?

Common 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.

Read the original research

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

View on PubMed ↗Publisher’s paper ↗

Citation

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