Glucose-lowering agents and reduced risk of incident non-alcoholic fatty liver disease: new insights

Maybe, given the multiple pathways involved in the NAFLD pathogenesis and the single response from single- agent therapies (that stands from 30% to 50%) observed in the RCTs published so far (3), the combination of different agents with various mechanisms of action may be the best way to treat NAFLD and its advanced forms (11). In this regard, for instance, the GLP-1 RA, semaglutide, is being investigated in combination with the nonsteroidal Farnesoid X receptor (FXR) agonist, cilofexor, and with the acetyl- CoA carboxylase inhibitor, firsocostat, in a phase 2 proof- of-concept trial (NCT03987074). Semaglutide is also being investigated in combination with empagliflozin (gliflozin) in a placebo-controlled, double-blind, randomized, 3-arm parallel group trial (NCT04639414). Moreover, considering the heterogeneity of NAFLD patients, it might be even more suitable to identify specific individuals for a definite therapeutic strategy (11). However, the research on this topic is still at the beginning and further studies are needed to improve our understanding for intercepting NAFLD patients who would have a higher probability of treatment response with a specific agent as monotherapy or, better, with a combination therapy (3).