Comparative effectiveness of sodium‐glucose cotransporter‐2 inhibitors and dipeptidyl peptidase‐4 inhibitors in improvement of fatty liver index in patients with type 2 diabetes mellitus and metabolic dysfunction‐associated steatotic liver disease: A retrospective nationwide claims database study in Japan

Abstract Aim To date, there are limited clinical studies and real‐world evidence investigating whether sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) are associated with improved hepatic steatosis. This study aimed to evaluate the effectiveness of SGLT2i compared with that of dipeptidyl peptidase‐4 inhibitors (DPP4i) in improving the fatty liver index (FLI) in patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction‐associated steatotic liver disease (MASLD). Materials and Methods This retrospective cohort study included new users of SGLT2i or DPP4i with T2DM and MASLD from a large claims database (JMDC Claims Database). The primary outcome was the incidence of improvement of the FLI. Cox proportional hazard models, weighted using propensity scores for predicting the initiation of treatment, were fitted to estimate hazard ratios with 95% confidence intervals (CIs). Time‐course changes in the FLI values were also assessed. Results This study included 9127 SGLT2i and 12 286 DPP4i initiators. SGLT2i showed a higher incidence of improvement in the FLI (≥30%, ≥40% and ≥50% reduction from baseline FLI) compared with DPP4i, and the weighted hazard ratios were 1.27 (95% CI 1.18‐1.38), 1.24 (95% CI 1.13‐1.37) and 1.19 (95% CI 1.05‐1.33), respectively. SGLT2i indicated a greater decreased in FLI values compared with DPP4i at up to 3 years of the follow‐up period. Conclusion SGLT2is use appeared to be associated with a greater improvement of the FLI than DPP4i use in patients with T2DM and MASLD. In the absence of direct head‐to‐head comparisons from clinical studies, our study, using real‐world data, may support physicians' decision‐making in clinical practice.