Efficacy and safety of liraglutide in non-alcoholic fatty liver disease with or without type 2 diabetes: A systematic review and meta-analysis.

AIMS: To comprehensively assess the efficacy and safety of liraglutide on metabolic and hepatic outcomes in patients with non-alcoholic fatty liver disease (NAFLD), with or without type 2 diabetes mellitus (T2DM), based on randomised controlled trials (RCTs). MATERIALS AND METHODS: Electronic databases (PubMed, Web of Science, Cochrane Library and Embase) were systematically searched for randomised RCTs evaluating liraglutide in the treatment of NAFLD. Outcome measures included body mass index (BMI), glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and adverse events (AEs). RESULTS: Eight RCTs (with an overall moderate risk of bias as assessed by the Cochrane Risk of Bias tool) involving 478 participants were included in the analysis. The meta-analysis results demonstrated that liraglutide significantly improved BMI (standardised mean difference [SMD]: -0.85; 95% confidence interval [CI]: -1.04 to -0.66), FPG (SMD: -1.22; 95% CI: -1.97 to -0.46), and GGT (SMD: -1.10; 95% CI: -1.48 to -0.72; p < 0.00001) in patients with NAFLD, regardless of T2DM comorbidity. Furthermore, liraglutide showed positive effects on ALT (SMD: -0.44; 95% CI: -0.80 to -0.08) and TG (SMD: -1.08; 95% CI: -1.97 to -0.19) specifically in patients with NAFLD comorbid with T2DM. However, the effect of liraglutide on HbA1c was not statistically significant (SMD: 0.14; 95% CI: -0.39 to 0.67). Regarding safety, liraglutide was associated with a higher incidence of adverse events, primarily gastrointestinal disorders such as nausea and diarrhoea, though these were mostly transient. CONCLUSIONS: Liraglutide demonstrates beneficial effects on BMI, FPG and GGT in patients with NAFLD with or without comorbid T2DM. It also shows positive effects on ALT and TG in patients with NAFLD and T2DM. While the treatment was associated with a higher burden of mostly manageable gastrointestinal adverse events, the findings of this study warrant further validation in prospective high-quality studies.