Clinical Report: Revising the Pharmacotherapy Approach for MASH

Overview

This network meta-analysis evaluates the efficacy and tolerability of various pharmacological agents for metabolic dysfunction-associated steatohepatitis (MASH), highlighting SGLT2 inhibitors and FGF21 analogs as leading options for fibrosis improvement. The findings suggest a need for further Phase 3 trials to confirm these results.

Background

MASH is a significant global health issue, with liver fibrosis being a key predictor of adverse outcomes such as cirrhosis and liver-related mortality. The recent approval of new pharmacological agents has the potential to transform treatment strategies for MASH, yet gaps in evidence regarding the comparative effectiveness of these agents remain.

Data Highlights

Key Findings

• FGF21 analogs showed the highest efficacy for fibrosis improvement (RR 2.22).
• SGLT2 inhibitors ranked closely for fibrosis improvement (RR 2.27).
• GLP-1/GIP dual agonists demonstrated the highest efficacy for MASH resolution (RR 5.21).
• SGLT2 inhibitors occupied the 'Optimal Zone' for efficacy and tolerability in cluster analysis.
• Robustness of findings was confirmed through sensitivity analyses excluding small-scale studies.

Clinical Implications

The findings suggest that SGLT2 inhibitors may serve as a promising oral treatment option for MASH, warranting further investigation in larger Phase 3 trials. Clinicians should consider the evolving pharmacological landscape when managing patients with MASH.

Conclusion

This analysis highlights the potential of SGLT2 inhibitors and FGF21 analogs in treating MASH, emphasizing the need for further research to validate these findings.

Related Resources & Content

1. Clinical Research in Cardiology, 2021 -- Impact of Receptor Specificity on the Advantages of SGLT2 Inhibitors for Heart Failure Patients: A Systematic Review and Comparative Efficacy Network Meta-Analysis
2. The New Gastroenterologist, 2025 -- Identifying Optimal Approaches for Managing MASLD
3. Frontiers in Cardiovascular Medicine, 2026 -- Evaluation of the therapeutic effect of new hypoglycemic drugs on patients with heart failure with reduced ejection fraction and type 2 diabetes: a systematic review and network meta-analysis
4. Clinical Care Pathway for the Risk Stratification and Management of Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease - ScienceDirect
5. Clinical Assessment and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease | AASLD
6. Drug Trials Snapshots: REZDIFFRA | FDA
7. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis | New England Journal of Medicine
8. Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis | New England Journal of Medicine
9. Frontiers in Endocrinology — Clinical efficacy, safety, and predictors of treatment response to SGLT2 versus DPP-4 inhibitors in type 2 diabetes: a retrospective comparative study
10. Clinical Care Pathway for the Risk Stratification and Management of Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease - ScienceDirect
11. Clinical Assessment and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease | AASLD
12. Drug Trials Snapshots: REZDIFFRA | FDA
13. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis | New England Journal of Medicine
14. Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis | New England Journal of Medicine
15. Safety and efficacy of once-weekly efruxifermin versus placebo in metabolic dysfunction-associated steatohepatitis (HARMONY): 96-week results from a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial - ScienceDirect
16. Effect of dapagliflozin on metabolic dysfunction-associated steatohepatitis: multicentre, double blind, randomised, placebo controlled trial - PMC
17. MASH treatments compared in network meta-analysis | ACP Gastroenterology Monthly
18. A Randomized, Placebo-Controlled, Phase 2 Study of the Safety and Efficacy of Combination Treatment with Semaglutide, Cilofexor and Firsocostat in Patients With Compensated Cirrhosis Due to Metabolic Dysfunction-Associated Steatohepatitis (WAYFIND)