AbstractAimsEmpagliflozin treatment reduced liver fat in small type 2 diabetes cohorts. This post‐hoc study evaluated effects of empagliflozin on risk for non‐alcoholic fatty liver disease‐related steatosis and fibrosis, as well as the relationship between risk categories and cardiorenal outcomes in the randomized, placebo‐controlled EMPA‐REG OUTCOME trial.Materials and methodsEMPA‐REG OUTCOME treated 7020 people with type 2 diabetes and cardiovascular disease with 10/25 mg/day empagliflozin or placebo. For this analysis, the Dallas steatosis index, hepatic steatosis index, non‐alcoholic fatty liver disease fibrosis score and Fibrosis‐4 score were calculated to assess steatosis and fibrosis risk. Changes from baseline in scores were examined by mixed model repeated measures and their associations with cardiorenal outcomes and mortality by Cox regression.ResultsAt baseline, 73% and 84% of participants had high steatosis risk by Dallas steatosis index and hepatic steatosis index, whereas 23% and 4% had a high risk of advanced fibrosis by non‐alcoholic fatty liver disease fibrosis score and Fibrosis‐4 score. Percentages of people at high steatosis risk slightly decreased with empagliflozin only, whereas empagliflozin did not improve percentages of individuals at high fibrosis risk over time compared with placebo. The high risk of advanced fibrosis at baseline related to higher risk for cardiovascular events. Effects of empagliflozin on cardiorenal and all‐cause mortality outcomes were consistent across all risk groups.ConclusionsEmpagliflozin may reduce steatosis but not fibrosis risk in individuals with type 2 diabetes and cardiovascular disease. The improvements in cardiorenal outcomes and mortality associated with empagliflozin therapy appear to be independent of steatosis and fibrosis risk.