Glucagon-like peptide-1 receptor agonists improve MASH and liver fibrosis: a meta-analysis of randomized controlled trials
Glucagon-like peptide-1 receptor agonists improve MASH and liver fibrosis: a meta-analysis of randomized controlled trials
Background/Aims: There is uncertainty regarding the hepatic efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in metabolic dysfunction-associated steatotic liver disease (MASLD) or steatohepatitis (MASH). We performed a meta-analysis of randomised controlled trials (RCTs) to examine the efficacy of GLP-1RAs in treating MASLD or MASH.
Methods: we systematically searched three electronic databases from inception until April 2025 to identify RCTs examining the efficacy of GLP-1RAs for the treatment of MASLD or MASH. The outcome measures included MASH resolution without worsening of fibrosis or improvement in at least one stage of fibrosis without worsening of MASH, along with reductions in liver fat content measured using magnetic resonance-based techniques. Meta-analysis was conducted using random-effects models.
Results: we identified 13 phase 2 or phase 3 RCTs (1811 participants). These trials diagnosed MASLD or MASH through liver biopsy (n = 4) or magnetic resonance-based techniques (n = 9). Regardless of diabetes status, among individuals with MASH and moderate-to-advanced fibrosis, GLP-1RAs (especially semaglutide 2.4 mg/week) for up to 72 weeks were superior to placebo in achieving MASH resolution (n = 3 RCTs; pooled random-effects odds ratio 3.48, 95% CI 2.69–4.51; I2 = 0%), and in improving liver fibrosis (pooled odds ratio 1.79, 95% CI 1.37–2.35; I2 = 0%). Among individuals with MASH-related compensated cirrhosis (n = 1 RCT available only), semaglutide did not lead to MASH resolution or improved fibrosis compared to placebo. Furthermore, GLP-1RAs reduced magnetic resonance-measured liver fat content (n = 9; pooled mean difference: −4.50%, 95% CI −6.60 to −2.40%; I2 = 95.9%).
Conclusions: GLP-1RAs are a promising treatment option for MASLD or MASH. Further research is needed to evaluate the long-term effects of GLP-1RAs on liver-related clinical events.
GLP-1 receptor agonists, incretin-based therapy, metabolic dysfunction-associated steatohepatitis, metabolic dysfunction-associated steatotic liver disease
e70256
Mantovani, Alessandro
bde31cfa-0bff-45b2-a532-fb048eedc763
Morandin, Riccardo
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Fiorio, Veronica
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Lando, Maria Giovanna
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Stefan, Norbert
a5c0eaff-3132-45dd-8fe2-df8b59b456a6
Tilg, Herbert
907cf5a5-322f-4a11-91cc-18eb35814d12
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Targher, Giovanni
d71dcd10-dbf1-477c-9301-aa9dc34b8dc7
1 September 2025
Mantovani, Alessandro
bde31cfa-0bff-45b2-a532-fb048eedc763
Morandin, Riccardo
c0ad52d5-dfca-4626-a60b-3f25ff3c33f9
Fiorio, Veronica
10b000eb-fc21-451e-a4e0-a8871ff7f34a
Lando, Maria Giovanna
bc76e11d-3439-4374-b477-96dc52e4b5a5
Stefan, Norbert
a5c0eaff-3132-45dd-8fe2-df8b59b456a6
Tilg, Herbert
907cf5a5-322f-4a11-91cc-18eb35814d12
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Targher, Giovanni
d71dcd10-dbf1-477c-9301-aa9dc34b8dc7
Mantovani, Alessandro, Morandin, Riccardo, Fiorio, Veronica, Lando, Maria Giovanna, Stefan, Norbert, Tilg, Herbert, Byrne, Christopher D. and Targher, Giovanni
(2025)
Glucagon-like peptide-1 receptor agonists improve MASH and liver fibrosis: a meta-analysis of randomized controlled trials.
Liver International, 45 (9), , [e70256].
(doi:10.1111/liv.70256).
Abstract
Background/Aims: There is uncertainty regarding the hepatic efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in metabolic dysfunction-associated steatotic liver disease (MASLD) or steatohepatitis (MASH). We performed a meta-analysis of randomised controlled trials (RCTs) to examine the efficacy of GLP-1RAs in treating MASLD or MASH.
Methods: we systematically searched three electronic databases from inception until April 2025 to identify RCTs examining the efficacy of GLP-1RAs for the treatment of MASLD or MASH. The outcome measures included MASH resolution without worsening of fibrosis or improvement in at least one stage of fibrosis without worsening of MASH, along with reductions in liver fat content measured using magnetic resonance-based techniques. Meta-analysis was conducted using random-effects models.
Results: we identified 13 phase 2 or phase 3 RCTs (1811 participants). These trials diagnosed MASLD or MASH through liver biopsy (n = 4) or magnetic resonance-based techniques (n = 9). Regardless of diabetes status, among individuals with MASH and moderate-to-advanced fibrosis, GLP-1RAs (especially semaglutide 2.4 mg/week) for up to 72 weeks were superior to placebo in achieving MASH resolution (n = 3 RCTs; pooled random-effects odds ratio 3.48, 95% CI 2.69–4.51; I2 = 0%), and in improving liver fibrosis (pooled odds ratio 1.79, 95% CI 1.37–2.35; I2 = 0%). Among individuals with MASH-related compensated cirrhosis (n = 1 RCT available only), semaglutide did not lead to MASH resolution or improved fibrosis compared to placebo. Furthermore, GLP-1RAs reduced magnetic resonance-measured liver fat content (n = 9; pooled mean difference: −4.50%, 95% CI −6.60 to −2.40%; I2 = 95.9%).
Conclusions: GLP-1RAs are a promising treatment option for MASLD or MASH. Further research is needed to evaluate the long-term effects of GLP-1RAs on liver-related clinical events.
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Fig 2_fibrosis improvement
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Fig 3_MRI liver fat
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Fig 1_mash resolution
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Accepted/In Press date: 23 July 2025
Published date: 1 September 2025
Keywords:
GLP-1 receptor agonists, incretin-based therapy, metabolic dysfunction-associated steatohepatitis, metabolic dysfunction-associated steatotic liver disease
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Local EPrints ID: 504673
URI: http://eprints.soton.ac.uk/id/eprint/504673
ISSN: 1478-3223
PURE UUID: eadd402a-3ca4-4d37-a37f-5de7987e929a
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Date deposited: 17 Sep 2025 16:46
Last modified: 20 Sep 2025 01:38
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Contributors
Author:
Alessandro Mantovani
Author:
Riccardo Morandin
Author:
Veronica Fiorio
Author:
Maria Giovanna Lando
Author:
Norbert Stefan
Author:
Herbert Tilg
Author:
Giovanni Targher
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