FGF-21 analogues for treatment of non-alcoholic steatohepatitis and fibrosis: a meta-analysis with fragility index of phase 2 randomised placebo-controlled trials

We have read with interest the excellent review by Trauner and Fuchs on the novel therapeutic approaches that are currently developed for treating non-alcoholic steatohepatitis (NASH).1 Although there are no licensed pharmacotherapies for NASH, long-acting fibroblast growth factor-21 (FGF-21) analogues are being evaluated to treat NASH because FGF-21 is a pleotropic liver-derived hormone regulating lipid metabolism, insulin sensitivity and energy homeostasis, all mechanisms closely implicated in NASH development.2 To quantify the magnitude of the possible hepatoprotective effects of FGF-21 analogues, we systematically searched three electronic databases from the inception date to 1 September 2023 to identify phase-2 randomised controlled trials (RCTs) examining the efficacy of FGF-21 analogues on the US Food and Drug Administration defined histological endpoints for conditional approval of new drugs for NASH, that is, NASH resolution without worsening of fibrosis or ≥1 stage fibrosis improvement without worsening of NASH. We also calculated the fragility index (FI) to establish the robustness of the trial’s data.3 More details of the systematic review are reported in online supplemental material.