1. Introduction
Non-alcoholic steatohepatitis (NASH) represents an advanced form of non-alcoholic fatty liver disease (NAFLD), characterized by inflammation and fibrosis in the liver.1 Currently, it affects approximately 20 to 30% of the global population, emerging as the leading hepatic cause of morbidity and mortality.2 The significant increase in the incidence of this condition and its potentially lethal complications, such as cirrhosis or hepatocellular carcinoma, highlight it as a significant challenge for public health.3,4 It is important to emphasize that, to date, there are no drugs approved by the Food and Drug Administration specifically intended for the treatment of NASH, which emphasizes the urgency of implementing effective strategies to address this condition.5
Fibroblast growth factor 21 (FGF21), a hormone that regulates lipid and glucose metabolism, has shown hepatoprotective effects in preclinical studies. These findings suggest a potential therapeutic role for FGF21 in NAFLD, paving the way for the development of more effective therapeutic strategies in addressing this condition.6,7 Current literature and clinical practice offer promising perspectives on the therapeutic potential of FGF21 analogs in NAFLD, highlighting their role as mediators of homeostasis and inflammatory process in the disease metabolism. These analogs demonstrate the ability to reduce liver fat, prevent hepatocyte damage and suppress inflammation.8,9 However, the variability in individual responses and the lack of consensus on assessment criteria pose significant challenges to the clinical implementation of these therapies.
Recently, two large, planned trials have investigated the role of FG21 analogs as a therapy of choice for clinical and laboratory benefits in patients with NASH (Non-Alcoholic Steatohepatitis). These studies have substantially increased the population of randomized patients receiving efruxifermin, pegbelfermin, or pegozafermin as a strategy for resolving NASH and improving metabolic profiles.10,11 Therefore, we aimed to perform a meta-analysis of Randomized Controlled Trials (RCTs) to assess the safety and efficacy of FGF21 analogs in the treatment of NASH.