Comparative effects between old and new antidiabetic agents on metabolic- associated fatty liver disease (MAFLD)

Type 2 diabetes (T2DM) and liver disease, mainly metabolic-associated fatty liver disease (MAFLD), previously named non-alcoholic fatty liver disease (NAFLD), coexist in many patients. While physicians were reluctant to use glucose-lowering agents other than insulin in patients with T2DM and liver disease for many decades, the scene changed in recent years. While metformin gave controversial results in patients with MAFLD, pioglitazone was the first to demonstrate unequivocal positive effects, but its use in clinical practice is limited by safety concerns. New glucose-lowering agents, both glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, raised new hope. Indeed, besides a good safety profile, these agents, which are associated with weight loss, pleitotropic effects and cardiorenal protection, have also proven their efficacy in improving MAFLD. The positive effects on liver fat content, hepatic enzymes used as markers of steatosis and indices of tissue inflammation are now well demonstrated, yet available data on fibrosis are more limited. Thus, more dedicated studies, using liver biopsies, are still warranted to demonstrate the efficacy of these two pharmacological classes in preventing the progression from simple steatosis to fibrosis/cirrhosis and further confirm this new opportunity for the management of patients with T2DM and MAFLD.