Optimized strategy among diet, exercise, and pharmacological interventions for nonalcoholic fatty liver disease: A network meta‐analysis of randomized controlled trials

Background: Emerging treatment methods, including exercise, diet, and drugs, for nonalcoholic fatty liver disease (NAFLD) have been proposed. However, the differences in their efficacy have not been determined. We aimed to compare the effects of these treatments excluding surgery via a systematic review and network meta-analysis of randomized controlled trials (RCTs).Data Source: The data sources included PubMed, Embase, Web of Science and Cochrane up to February 1st, 2023. The endpoints consisted of body mass index (BMI), serum markers of metabolism and liver injury markers (triglycerides, low-density lipoprotein, alanine aminotransferase, glutamyltransferase, and insulin resistance), liver fat content and stiffness as assessed by ultrasound/magnetic resonance/liver biopsy-based techniques.Results: A total of 174 studies with 10,183 patients were included in this meta-analysis (34 types of interventions, 1180 patients receiving diet intervention, 1154 patients receiving exercise intervention, 4708 patients receiving drugs drugs and 3141 patients as the control group). In terms of improving BMI, Pan agnosit of PPAR is the best treatment with the highest SUCRA (surface under the cumulative ranking) of 84.8% (mean=-3·40, 95% CI – 5·55, -1·24) by the comparative effectiveness ranking. GLP-1 (glucagon-like peptide-1) has the best effect in improving the liver fat content based on the MRI-PDFF (MRI-derived proton density fat fraction) steatosis score (SUCRA 99·7%, mean -2·19, 95% CI -2·90, -1·48) and ballooning score (SUCRA 61·2% , mean=-0·82, 95% CI – 4·46, 2·83).Conclusions: Pan agnosit of PPAR was the most efficacious regimen in lowering BMIs whereas GLP-1R agonists achieved the highest efficacy of steatosis improvement in this network meta-analysis.Funding: This research was funded by the National Natural Science Foundation of China (82100648, 81870404).Declaration of Interest: All authors declare that they have no competing interests.