Supplementary Material for: Efficacy and safety of FGF21 analogues for metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis

Introduction: Fibroblast growth factor 21 (FGF21) analogues may benefit patients with metabolic dysfunction-associated steatohepatitis (MASH). We aimed to compare the efficacy and safety of FGF21 analogues versus placebo for treating patients with MASH in randomized controlled trials (RCTs). Methods: We searched PubMed, Embase, and the Cochrane Library. Primary outcomes were fibrosis improvement ≥1 stage without worsening of MASH and MASH resolution without worsening of fibrosis. Secondary outcomes were relative reduction ≥30% of the hepatic fat fraction (HFF) measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) and adverse events (AEs). Results: We included 7 RCTs (886 patients). FGF21 analogues had a higher probability of fibrosis improvement ≥1 stage without worsening of MASH (RR 1.54; 95%CI 1.07, 2.22), MASH resolution without worsening of fibrosis (RR 3.31; 95%CI 1.80, 6.06), and reduction ≥30% in the HFF by MRI-PDFF (RR 3.03; 95%CI 2.12, 4.33) than placebo, without significant difference in the risk of AEs. Subgroup analyses by the stage of fibrosis showed FGF21 analogues improved fibrosis only among patients with fibrosis stages F1-F3. Conclusion: FGF21 analogues appear to be an effective and safe treatment option for patients with MASH, although the impact on fibrosis improvement may be limited to non-cirrhotic patients.