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
Lili Liu, Ying Xia, Bian Wang, Yiyu Zhang
Abstract
ABSTRACT 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 2 = 12.9%) and could decrease the levels of LFC (weighted mean difference [WMD] −4.34%, 95% CI −5.88 to −2.81, I 2 = 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 2 = 0%). 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.