Effects of Tirzepatide on Patients With Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Retrospective Cohort Study.

BACKGROUND:  Tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GLP-1) receptor agonist, has recently been introduced in Japan; however, there are limited studies on its effectiveness in Japanese patients with type 2 diabetes diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD). PATIENTS AND METHODS:  This retrospective cohort study was conducted among 54 Japanese patients (29 men and 25 women) with type 2 diabetes and MASLD to assess the impact of switching from a GLP-1 receptor agonist (GLP-1RA) to tirzepatide. Before the switch, either dulaglutide or semaglutide was used as the GLP-1RA. Clinical findings were analyzed before and six months after switching to tirzepatide. Additionally, a multiple regression analysis was performed to determine whether characteristics and test results before switching to tirzepatide could predict the weight loss and MASLD suppression six months after initiation. The fatty liver index and fibrosis-4 (FIB-4) index were utilized as MASLD indicators. High-sensitivity C-reactive protein (hsCRP) levels from residual serum were measured as an indicator of chronic inflammation. RESULTS:  Six months after switching to tirzepatide, significant reductions in body weight, hemoglobin A1c (HbA1c) level, fatty liver index, FIB-4 index, and hsCRP level were observed. The multiple regression analysis identified age, duration of type 2 diabetes, and HbA1c levels before the switch as significant independent predictors of weight loss rate. Also, the multiple regression analysis suggested that age before the switch may serve as a useful predictor of a decrease in fatty liver index. The effect of tirzepatide on appetite was less pronounced in the group that had used semaglutide before the switch compared with the group that had used dulaglutide; however, even in the semaglutide group, significant reductions in body weight, HbA1c levels, fatty liver index, and FIB-4 index were noted six months after the switch. CONCLUSIONS:  This study suggested the efficacy of switching from GLP-1RAs to tirzepatide among Japanese patients with type 2 diabetes and MASLD. Predictors of weight loss and fatty liver index reduction after switching to tirzepatide were identified. Additionally, we found that the therapeutic effect of tirzepatide can be expected even in patients who were using semaglutide before the switch.