GLP-1 receptor agonists improved resolution without fibrosis worsening but did not significantly improve fibrosis.
Evidence
This PRISMA 2020 systematic review and meta-analysis included 25 randomized controlled trials with 2481 participants, finding MASH resolution benefit across 7 RCTs (OR=4.04; 95% CI 2.69-6.05) and no significant fibrosis improvement across 5 RCTs (OR=1.54; 95% CI 0.95-2.48).
Caveat
Trial sequential analysis found sufficient evidence for MASH resolution but not fibrosis improvement, leaving antifibrotic effects uncertain.
Simplified
BACKGROUND: Metabolic dysfunction-associated steatohepatitis () is a leading cause of chronic liver disease globally, with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show potential for MASH due to their metabolic benefits, but evidence on histological outcomes remains inconclusive.
METHODS: We conducted a PRISMA 2020-compliant systematic review and meta-analysis, including 25 randomized controlled trials (RCTs, n=2481). Primary outcomes were resolution of MASH without fibrosis worsening and fibrosis improvement without steatohepatitis worsening. Secondary outcomes included anthropometric and biochemical parameters. Risk of bias was assessed via ROB 2, and evidence certainty via GRADE. Trial sequential analysis (TSA) addressed random errors.
RESULTS: GLP-1 RAs significantly increased MASH resolution without fibrosis worsening (OR=4.04; 95% CI [2.69-6.05]; P<0.00001; 7 RCTs, n=1456). No significant improvement in fibrosis was observed (OR=1.54; 95% CI [0.95-2.48]; P=0.08; 5 RCTs, n=1277). Secondary outcomes showed reduced BMI (MD=-0.52 kg/m; P=0.05) but no significant changes in weight, waist circumference, liver enzymes, or lipids. TSA confirmed sufficient evidence for MASH resolution (RIS=197) but not fibrosis improvement (RIS=1693). GRADE indicated high certainty for primary outcomes. 2
CONCLUSION: GLP-1 RAs promote MASH resolution but do not significantly improve fibrosis. Their benefits appear to be driven by metabolic mechanisms rather than direct antifibrotic effects. Larger RCTs targeting fibrosis endpoints are warranted.
TRIAL REGISTRATION: The protocol for our meta-analysis and systematic review was registered and recorded in PROSPERO (registration no. CRD420251090801).
Key numbers
4.04
Increase in Resolution Odds
Odds ratio for resolution without fibrosis worsening from 7 RCTs involving 1456 patients.
1.54
No Significant Fibrosis Improvement
Odds ratio for fibrosis improvement without worsening of steatohepatitis from 5 RCTs involving 1277 patients.
-0.52 kg/m
Reduction in BMI
Mean difference in BMI from secondary outcomes.
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