Abstract
OBJECTIVE: This study aimed to conduct the first network meta-analysis (NMA) comparing the effectiveness of sodium-glucose transporter 2 (SGLT-2) inhibitors-dapagliflozin, empagliflozin, and ipragliflozin-in improving liver-related and metabolic outcomes in patients with nonalcoholic fatty liver disease (NAFLD), utilizing a robust Bayesian NMA framework. METHODS: We conducted a systematic review and Bayesian NMA of randomized controlled trials (RCTs) up to December 31, 2024, following Preferred Reporting Items for Systematic Reviews and Network Meta-Analyses guidelines. Databases (PubMed, Cochrane Library, Scopus, Embase) were searched for RCTs involving NAFLD patients (with or without type 2 diabetes) treated with SGLT-2 inhibitors versus placebo/standard treatments. Outcomes included alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, fibrosis-4 score, body weight, and fasting plasma glucose. A random-effects Bayesian NMA was performed using a Markov Chain Monte Carlo method, with treatments ranked via Surface Under the Cumulative Ranking Curve (SUCRA) scores. RESULTS: Eleven RCTs (805 patients) were included. Dapagliflozin led in alanine aminotransferase (mean difference [MD]: -11.35 IU/L, 95% CrI: -18.39 to -4.19, SUCRA: 84.87%), aspartate aminotransferase (MD: -7.96 IU/L, 95% CrI: -15.69 to -0.18, SUCRA: 81.70%), and body weight reduction (MD: -3.60 kg, 95% CrI: -5.92 to -1.64, SUCRA: 88.88%). Ipragliflozin excelled in gamma-glutamyl transferase (MD: -15.19 IU/L, 95% CrI: -31.25 to -2.11, SUCRA: 81.35%) and fasting plasma glucose reduction (MD: -2.20 mmol/L, 95% CrI: -9.88 to 5.30, SUCRA: 59.79%). Empagliflozin topped fibrosis-4 score reduction (MD: -0.12, 95% CrI: -0.42 to 0.13, SUCRA: 73.27%). CONCLUSION: SGLT-2 inhibitors significantly improve liver and metabolic outcomes in NAFLD, with dapagliflozin, ipragliflozin, and empagliflozin offering distinct benefits, supporting personalized treatment strategies.