Efficacy and safety of GLP-1 receptor agonists in metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis of randomized controlled trials

Chia Siang Kow; Kaeshaelya Thiruchelvam; Syed Shahzad Hasan; Abdullah Faiz Zaihan

doi:10.1177/20101058261424018

Efficacy and safety of GLP-1 receptor agonists in metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis of randomized controlled trials

Chia Siang Kow, Kaeshaelya Thiruchelvam, Syed Shahzad Hasan, Abdullah Faiz Zaihan

Research output: Contribution to journal › Review article › peer-review

Abstract

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disorder that increases the risk of cirrhosis and liver-related death. Despite its growing prevalence, effective pharmacological treatments remain limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as potential agents capable of improving liver histology in patients with MASH.

Objective: This study aimed to evaluate the efficacy and safety of GLP-1 receptor agonists in promoting histological resolution of MASH and improving liver fibrosis in adults with biopsy-confirmed disease.

Methods: We systematically searched PubMed, Embase, Cochrane CENTRAL, and Scopus from inception to 27 June 2025 for randomized controlled trials comparing GLP-1 receptor agonists with placebo in adults with biopsy-proven MASH. The primary endpoint was MASH resolution without fibrosis progression; secondary endpoints were ≥1-stage fibrosis improvement and any adverse events. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool. Pooled risk ratios (RRs) were estimated using a random-effects model.

Results: Three RCTs with a total of 1,172 participants were included. Treatment with GLP-1RAs significantly increased the likelihood of MASH resolution without fibrosis progression (RR = 2.04; 95% CI: 1.53–2.72; I² = 19%). GLP-1RAs also improved fibrosis without worsening of MASH (RR = 1.53; 95% CI: 1.24–1.89; I² = 0%). A modest rise in overall adverse events was observed (RR = 1.08; 95% CI: 1.02–1.14; I² = 9%), primarily reflecting mild to moderate gastrointestinal symptoms.

Conclusion: GLP-1 receptor agonists, particularly semaglutide and liraglutide, significantly enhance histologic outcomes in patients with biopsy-confirmed MASH while maintaining a favorable safety profile. These findings highlight the potential of GLP-1RAs as disease-modifying agents for MASH, especially in individuals with metabolic comorbidities.

Original language	English
Number of pages	8
Journal	Proceedings of Singapore Healthcare
Volume	35
Early online date	4 Feb 2026
DOIs	https://doi.org/10.1177/20101058261424018
Publication status	E-pub ahead of print - 4 Feb 2026

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SDG 3 Good Health and Well-being

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@article{2988c878ffaf4fa4b613c3725362e0fb,

title = "Efficacy and safety of GLP-1 receptor agonists in metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis of randomized controlled trials",

abstract = "Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disorder that increases the risk of cirrhosis and liver-related death. Despite its growing prevalence, effective pharmacological treatments remain limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as potential agents capable of improving liver histology in patients with MASH. Objective: This study aimed to evaluate the efficacy and safety of GLP-1 receptor agonists in promoting histological resolution of MASH and improving liver fibrosis in adults with biopsy-confirmed disease. Methods: We systematically searched PubMed, Embase, Cochrane CENTRAL, and Scopus from inception to 27 June 2025 for randomized controlled trials comparing GLP-1 receptor agonists with placebo in adults with biopsy-proven MASH. The primary endpoint was MASH resolution without fibrosis progression; secondary endpoints were ≥1-stage fibrosis improvement and any adverse events. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool. Pooled risk ratios (RRs) were estimated using a random-effects model. Results: Three RCTs with a total of 1,172 participants were included. Treatment with GLP-1RAs significantly increased the likelihood of MASH resolution without fibrosis progression (RR = 2.04; 95\% CI: 1.53–2.72; I2 = 19\%). GLP-1RAs also improved fibrosis without worsening of MASH (RR = 1.53; 95\% CI: 1.24–1.89; I2 = 0\%). A modest rise in overall adverse events was observed (RR = 1.08; 95\% CI: 1.02–1.14; I2 = 9\%), primarily reflecting mild to moderate gastrointestinal symptoms. Conclusion: GLP-1 receptor agonists, particularly semaglutide and liraglutide, significantly enhance histologic outcomes in patients with biopsy-confirmed MASH while maintaining a favorable safety profile. These findings highlight the potential of GLP-1RAs as disease-modifying agents for MASH, especially in individuals with metabolic comorbidities.",

keywords = "cardiometabolic liver disease, fatty liver disease, histologic endpoint, incretin-based therapy, insulin resistance, liver biopsy trials, non-cirrhotic steatohepatitis",

author = "Kow, \{Chia Siang\} and Kaeshaelya Thiruchelvam and Hasan, \{Syed Shahzad\} and Zaihan, \{Abdullah Faiz\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).",

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language = "English",

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Efficacy and safety of GLP-1 receptor agonists in metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis of randomized controlled trials. / Kow, Chia Siang; Thiruchelvam, Kaeshaelya; Hasan, Syed Shahzad et al.
In: Proceedings of Singapore Healthcare, Vol. 35, 01.12.2026.

Research output: Contribution to journal › Review article › peer-review

TY - JOUR

T1 - Efficacy and safety of GLP-1 receptor agonists in metabolic dysfunction-associated steatohepatitis

T2 - A systematic review and meta-analysis of randomized controlled trials

AU - Kow, Chia Siang

AU - Thiruchelvam, Kaeshaelya

AU - Hasan, Syed Shahzad

AU - Zaihan, Abdullah Faiz

N1 - Publisher Copyright: © The Author(s) 2026. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

PY - 2026/2/4

Y1 - 2026/2/4

N2 - Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disorder that increases the risk of cirrhosis and liver-related death. Despite its growing prevalence, effective pharmacological treatments remain limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as potential agents capable of improving liver histology in patients with MASH. Objective: This study aimed to evaluate the efficacy and safety of GLP-1 receptor agonists in promoting histological resolution of MASH and improving liver fibrosis in adults with biopsy-confirmed disease. Methods: We systematically searched PubMed, Embase, Cochrane CENTRAL, and Scopus from inception to 27 June 2025 for randomized controlled trials comparing GLP-1 receptor agonists with placebo in adults with biopsy-proven MASH. The primary endpoint was MASH resolution without fibrosis progression; secondary endpoints were ≥1-stage fibrosis improvement and any adverse events. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool. Pooled risk ratios (RRs) were estimated using a random-effects model. Results: Three RCTs with a total of 1,172 participants were included. Treatment with GLP-1RAs significantly increased the likelihood of MASH resolution without fibrosis progression (RR = 2.04; 95% CI: 1.53–2.72; I2 = 19%). GLP-1RAs also improved fibrosis without worsening of MASH (RR = 1.53; 95% CI: 1.24–1.89; I2 = 0%). A modest rise in overall adverse events was observed (RR = 1.08; 95% CI: 1.02–1.14; I2 = 9%), primarily reflecting mild to moderate gastrointestinal symptoms. Conclusion: GLP-1 receptor agonists, particularly semaglutide and liraglutide, significantly enhance histologic outcomes in patients with biopsy-confirmed MASH while maintaining a favorable safety profile. These findings highlight the potential of GLP-1RAs as disease-modifying agents for MASH, especially in individuals with metabolic comorbidities.

AB - Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disorder that increases the risk of cirrhosis and liver-related death. Despite its growing prevalence, effective pharmacological treatments remain limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as potential agents capable of improving liver histology in patients with MASH. Objective: This study aimed to evaluate the efficacy and safety of GLP-1 receptor agonists in promoting histological resolution of MASH and improving liver fibrosis in adults with biopsy-confirmed disease. Methods: We systematically searched PubMed, Embase, Cochrane CENTRAL, and Scopus from inception to 27 June 2025 for randomized controlled trials comparing GLP-1 receptor agonists with placebo in adults with biopsy-proven MASH. The primary endpoint was MASH resolution without fibrosis progression; secondary endpoints were ≥1-stage fibrosis improvement and any adverse events. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool. Pooled risk ratios (RRs) were estimated using a random-effects model. Results: Three RCTs with a total of 1,172 participants were included. Treatment with GLP-1RAs significantly increased the likelihood of MASH resolution without fibrosis progression (RR = 2.04; 95% CI: 1.53–2.72; I2 = 19%). GLP-1RAs also improved fibrosis without worsening of MASH (RR = 1.53; 95% CI: 1.24–1.89; I2 = 0%). A modest rise in overall adverse events was observed (RR = 1.08; 95% CI: 1.02–1.14; I2 = 9%), primarily reflecting mild to moderate gastrointestinal symptoms. Conclusion: GLP-1 receptor agonists, particularly semaglutide and liraglutide, significantly enhance histologic outcomes in patients with biopsy-confirmed MASH while maintaining a favorable safety profile. These findings highlight the potential of GLP-1RAs as disease-modifying agents for MASH, especially in individuals with metabolic comorbidities.

KW - cardiometabolic liver disease

KW - fatty liver disease

KW - histologic endpoint

KW - incretin-based therapy

KW - insulin resistance

KW - liver biopsy trials

KW - non-cirrhotic steatohepatitis

UR - https://www.scopus.com/pages/publications/105047917928

U2 - 10.1177/20101058261424018

DO - 10.1177/20101058261424018

M3 - Review article

AN - SCOPUS:105047917928

SN - 2010-1058

VL - 35

JO - Proceedings of Singapore Healthcare

JF - Proceedings of Singapore Healthcare

ER -

Efficacy and safety of GLP-1 receptor agonists in metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis of randomized controlled trials

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