SynthesisFrontiers in endocrinology2026
Updating the MASH pharmacotherapy landscape: a network meta-analysis incorporating SGLT2 inhibitors and emerging combination therapies.
Synthesis in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- An updated overview of alkaloids for the prevention and treatment of metabolic dysfunction-associated steatotic liver disease.Frontiers in pharmacology · 2026Review
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3 authors.
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Abstract
Background: Multiple pharmacological agents targeting distinct pathways (e.g., GLP-1, FGF21, THR-β) show promise for metabolic dysfunction-associated steatohepatitis (MASH). However, while recent meta-analyses have established the efficacy of GLP-1 RAs and FGF21 analogs, they largely predate critical histological trials on SGLT2 inhibitors, leaving the comparative position of this highly accessible oral therapy undefined. We aimed to systematically rank the efficacy and tolerability of distinct pharmacological mechanisms for MASH and characterize their benefit-risk profiles through cluster analysis. Methods: We searched PubMed, Embase, Web of Science, Scopus, and Cochrane Library for Phase II/III randomized controlled trials (RCTs) involving adults with biopsy-proven MASH. The primary outcome was fibrosis improvement (≥1 stage reduction without MASH worsening). Secondary outcomes included MASH resolution and safety (discontinuation due to adverse events). A frequentist network meta-analysis (NMA) was performed. Results: We included 34 studies from 33 unique publications. For fibrosis improvement, FGF21 analogs (RR 2.22, 95% CI 1.40-3.54) and SGLT2 inhibitors (RR 2.27, 95% CI 1.22-4.17) ranked highest. Notably, SGLT2 inhibitors numerically outperformed the FDA-approved THR-β agonist (RR 1.61) and GLP-1 RAs (RR 1.51, 95% CI 1.09-2.10). For MASH resolution, GLP-1/GIP dual agonists (RR 5.21) and FGF21 analogs (RR 3.52) showed the highest efficacy, while SGLT2 inhibitors also yielded significant benefits (RR 2.92, 95% CI 1.18-7.26). In the two-dimensional cluster analysis evaluating the balance between fibrosis efficacy and tolerability, SGLT2 inhibitors numerically occupied the "Optimal Zone," though this finding is based on limited histological data. Sensitivity analyses excluding small-scale studies confirmed the robustness of these rankings. Conclusion: FGF21 analogs (RR 2.22, 95% CI 1.40-3.54) demonstrated the most robust evidence for fibrosis improvement. Preliminary evidence from a single pivotal trial suggests SGLT2 inhibitors (RR 2.27, 95% CI 1.22-4.17) may represent a promising oral option, though this requires confirmation in adequately powered Phase 3 trials. Further adequately powered Phase 3 trials are warranted to validate the magnitude of these histological benefits. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420261292638.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.