ReviewCureus2026
Efficacy and Safety of Dual and Triple Glucagon-Like Peptide-1-Based Polyagonists in Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Systematic Review and Meta-Analysis.
Review in Cureus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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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.
The trial behind it
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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Authors and funding
3 authors.
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Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), are strongly linked to obesity, insulin resistance, type 2 diabetes, and progressive liver fibrosis. Dual and triple glucagon-like peptide-1 (GLP-1)-based polyagonists may provide complementary hepatic and metabolic benefits, but their overall efficacy and safety have not been fully established. This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH. PubMed, the Cochrane Central Register of Controlled Trials, ScienceDirect, and Google Scholar were searched from inception through May 19, 2026. Dichotomous outcomes were pooled as risk ratios (RRs), and continuous outcomes were analyzed as mean differences (MDs), using random-effects models. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Six randomized controlled trials involving 961 participants were included. The included GLP-1-based polyagonists-tirzepatide, survodutide, pemvidutide, retatrutide, and cotadutide-significantly increased MASH resolution or histological improvement without worsening of fibrosis (RR 3.32, 95% CI 2.28-4.84; I² = 20%) and fibrosis improvement without worsening of MASH (RR 1.49, 95% CI 1.15-1.94; I² = 0%). Treatment also produced a greater relative reduction in liver fat content (MD -44.60 percentage points, 95% CI -51.17 to -38.04; I² = 0%) and increased the likelihood of achieving at least a 30% relative reduction in liver fat by magnetic resonance imaging-proton density fat fraction (RR 4.71, 95% CI 3.04-7.30; I² = 22%). Body weight was significantly reduced, although heterogeneity was considerable (MD -9.14 percentage points, 95% CI -17.38 to -0.91; I² = 98%). Nausea, diarrhea, and vomiting were more frequent with polyagonists, but no statistically significant differences were observed in serious adverse events or adverse events leading to treatment discontinuation. In conclusion, dual and triple GLP-1-based polyagonists improve histological and imaging-based hepatic outcomes in MASLD and MASH and may simultaneously address underlying metabolic dysfunction. However, gastrointestinal intolerance, pharmacological heterogeneity, the small number of trials, and limited follow-up warrant cautious interpretation. Larger phase 3 trials are needed to clarify drug-specific efficacy, long-term safety, and effects on liver-related and cardiovascular outcomes.
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