The benefit of metformin in the treatment of pediatric non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trials.

This is the first meta-analysis of the available literature about the efficacy of metformin exclusively in pediatric patients with non-alcoholic fatty liver disease (NAFLD). We conducted a systematic literature search through major electronic databases till March 12, 2023, investigating the efficacy and safety of metformin in pediatric NAFLD. Weighted mean difference (WD) and standard deviation (SD) were used for continuous outcomes. In total, 4 randomized controlled trials (RCTs) with 309 pediatric patients with NAFLD were included in the meta-analysis. Metformin could not reach a statistically significant improvement in alanine aminotransferase (ALT) levels [(ALT: WMD =  - 1.55 IU/L, 95% CI: - 5.38 to 2.28, I = 16%, p = 0.43), but had a statistically significant impact (p < 0.05) in insulin and HOMA-IR regulation, triglycerides, and high-density lipoprotein level improvement.   Conclusion: According to the data of this meta-analysis, treatment with metformin failed to statistically improve liver enzymes but may be beneficial in the improvement of lipid parameters and insulin metabolism regulation in pediatric patients with NAFLD. As there are not enough available studies in the literature, the influence of metformin on liver ultrasonography or histology in pediatric NAFLD should be further analyzed in future studies. What is Known: • Lifestyle modification with weight loss through physical activity and dietary modification is the recommended treatment option for pediatric NAFLD. • Metformin may reduce steatosis on ultrasound and may have a beneficial role in liver histology collated with insulin resistance improvement. What is New: • Metformin may improve insulin sensitivity and lipid parameters in children with obesity and NAFLD. • Metformin does not have a significant effect on transaminase levels in children with obesity and NAFLD.