Clinical efficacy of switching to tirzepatide in patients with type 2 diabetes and a high risk of metabolic dysfunction-associated steatotic liver disease undergoing GLP-1 receptor agonist therapy: Insights from the Hokkaido-TZP study

AIMS: To evaluate the clinical efficacy of switching from glucagon-like peptide-1 receptor agonists (GLP-1RAs) to tirzepatide in terms of metabolic and hepatic indices in patients with T2D at high risk of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This multicenter, retrospective study comprised secondary analysis of the Hokkaido-TZP study, focusing on a subpopulation of the original cohort at high risk of MASLD. We analyzed hepatic indices, including the Hepatic Steatosis Index (HSI) and Fibrosis-4 (FIB-4) index, over a 6-month period in 182 patients who switched from GLP-1RAs to tirzepatide. Patients were stratified into low-risk and high-risk groups based on baseline hepatic fibrosis status. RESULTS: Switching to tirzepatide significantly reduced glycated hemoglobin (HbA1c), body weight, and liver enzymes. HSI decreased in both groups, but a significant reduction in FIB-4 index was only observed in the high-risk group (P < 0.001). Improvements in hepatic indices were not correlated with changes in body mass index or HbA1c. Furthermore, baseline HSI was positively correlated with change in FIB-4 index (ρ = 0.234, P = 0.005). CONCLUSIONS: Switching from GLP-1RAs to tirzepatide was associated with incremental improvements in metabolic and hepatic indices in patients with T2D at high risk of MASLD, particularly in patients with high fibrosis risk, not clearly explained by changes in body weight.