Comparison of pharmacological therapies in metabolic dysfunction–associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis

Feb 4, 2025Hepatology (Baltimore, Md.)

Comparison of drug treatments for improving liver scarring and healing in metabolic fatty liver disease

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

A total of 29 randomized controlled trials involving 9,324 patients were analyzed for the efficacy of pharmacological agents in treating metabolic dysfunction-associated steatohepatitis ().

Pegozafermin, cilofexor + firsocostat, and cilofexor + selonsertib were ranked as the most effective for achieving fibrosis regression without worsening MASH.
Pegozafermin, survodutide, and tirzepatide were identified as the leading agents for achieving MASH resolution without worsening fibrosis.
Multiple pharmacological agents significantly outperformed placebo in both fibrosis regression and MASH resolution.
The study utilized surface under the cumulative ranking curve () analysis to evaluate the comparative efficacy of treatments.

AI simplified

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis () is a leading cause of liver disease. With the advent of multiple therapeutic targets in late-phase clinical drug development for MASH, there is a knowledge gap to better understand the comparative efficacy of various pharmacological agents. We conducted an updated network meta-analysis to evaluate the relative rank order of the different pharmacological agents for both fibrosis regression and MASH resolution.

APPROACH AND RESULTS: We searched PubMed and Embase databases from January 1, 2020 to December 1, 2024, for published randomized controlled trials comparing pharmacological interventions in patients with biopsy-proven MASH. The co-primary endpoints were fibrosis improvement ≥1 stage without MASH worsening and MASH resolution without worsening fibrosis. We conducted surface under the cumulative ranking curve () analysis. A total of 29 randomized controlled trials (n=9324) were included. Pegozafermin, cilofexor + firsocostat, denifanstat, survodutide, obeticholic acid, tirzepatide, resmetirom, and semaglutide were significantly better than placebo in achieving fibrosis regression without worsening MASH. Pegozafermin (SUCRA: 79.92), cilofexor + firsocostat (SUCRA: 71.38), and cilofexor + selonsertib (SUCRA: 69.11) were ranked the most effective interventions. Pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, semaglutide, pioglitazone, denifanstat, semaglutide, and lanifibranor were significantly better than placebo in achieving MASH resolution without worsening fibrosis. Pegozafermin (SUCRA: 91.75), survodutide (SUCRA: 90.87), and tirzepatide (SUCRA: 84.70) were ranked the most effective interventions for achieving MASH resolution without worsening fibrosis.

CONCLUSIONS: This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design.

Key numbers

79.92

Highest for Improvement

Rank for without worsening .

91.75

Highest for

Rank for without worsening .

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text ↗

Comparison of pharmacological therapies in metabolic dysfunction–associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis

Abstract

Key numbers

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Key numbers

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief