Efficacy of Incretin‐Based Therapies in Patients With Metabolic Dysfunction–Associated Steatotic Liver Disease: An Updated Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Sep 30, 2025Journal of gastroenterology and hepatology

Effectiveness of Incretin-Based Treatments in People with Fatty Liver Disease Linked to Metabolic Problems

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Abstract

The pooled data from 32 randomized controlled trials involving 2783 participants showed that GLP-1 receptor agonists (GLP-1 RAs) are associated with a 3.33 times greater resolution of metabolic dysfunction-associated steatohepatitis without worsening fibrosis.

GLP-1 RAs could decrease liver fat content by an average of 4.34%.
Significant reductions in liver function, serum triglycerides, body weight, body mass index (BMI), waist circumference, and glycosylated hemoglobin (HbA1c) were observed with GLP-1 RAs.
DPP-4 inhibitors had no significant impact on liver histology, liver fat content, or liver function, except for a reduction in HbA1c levels.
The use of GLP-1 RAs may be associated with an increased risk of gastrointestinal side effects.

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BACKGROUND AND AIM: Incretin-based therapies include glucagon-like peptide-1 single, dual, and triple receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors. This meta-analysis aimed to assess the efficacy of incretin-based therapies for metabolic dysfunction-associated steatotic liver disease.

METHODS: We searched PubMed, the Cochrane Library, and EMBASE for relevant studies published before December 6, 2024. The outcomes of interest included liver histology, liver fat content (LFC), liver function, serum lipid profiles, anthropometric profiles, glycosylated hemoglobin (HbA1c), and gastrointestinal side effects.

RESULTS: This meta-analysis included 32 randomized controlled trials with 2783 participants. The pooled data showed that GLP-1RAs were associated with resolution of metabolic dysfunction-associated steatohepatitis without worsening of fibrosis (relative risk [RR] 3.33, 95% confidence interval [CI] 2.38-4.66, I = 12.9%) and could decrease the levels of LFC (weighted mean difference [WMD] -4.34%, 95% CI -5.88 to -2.81, I = 95.3%). GLP-1 RAs could also significantly reduce liver function, serum triglyceride, body weight, body mass index (BMI), waist circumference (WC), and HbA1c while increasing the risk of gastrointestinal side effects. However, DPP-4 inhibitors had no significant effect on the above indicators except for HbA1c (WMD -0.62%, 95% CI -0.91 to -0.33, I = 0%). 2 2 2

CONCLUSION: This meta-analysis revealed that GLP-1RAs improved liver histology, LFC, liver function, and a variety of metabolic parameters in MASLD patients, whereas DPP-4 inhibitors had no apparent effect except for lowering HbA1c. Incretin-based therapies, especially GLP-1 RAs, may be candidate treatments for patients with MASLD but may increase the incidence of gastrointestinal side effects.

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Efficacy of Incretin‐Based Therapies in Patients With Metabolic Dysfunction–Associated Steatotic Liver Disease: An Updated Systematic Review and Meta‐Analysis of Randomized Controlled Trials

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