Tirzepatide and metabolic dysfunction-associated steatotic liver disease (MASLD) in obesity: a real-world multicenter study.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and is strongly associated with obesity, insulin resistance, and systemic inflammation. Tirzepatide, a dual GIP and GLP-1 receptor agonist, has shown significant effects on weight loss and metabolic control. However, real-world evidence on hepatic steatosis remains limited. The aim of this study was to evaluate the effect of tirzepatide treatment in patients with obesity and MASLD and to identify the clinical predictors of its hepatic effect. METHODS: In this retrospective study, 23 adults with overweight (BMI ≥27.0 kg/m²) with at least one weight-related comorbidity and patients with obesity (BMI ≥30.0 kg/m²) and MASLD (FLI > 44) were included. Participants received tirzepatide (2.5-5 mg weekly) for 3 months. Anthropometric, metabolic (glucose, insulin, HOMA-IR, HbA1c), lipid (cholesterol, HDL, LDL, triglycerides), inflammatory (hs-CRP), and liver enzyme (AST, ALT, GGT) parameters, together with FLI, were assessed at baseline and follow-up. Correlations of ΔFLI with clinical variables and multiple regression analyses were performed. RESULTS: After three months of treatment, significant reductions were observed in body weight, BMI, and waist circumference (all p < 0.001). Significant improvements were also found in fasting glucose (p = 0.001), HbA1c, insulin, and HOMA-IR (all p < 0.001). Inflammatory status improved, with a significant reduction in hs-CRP (p < 0.001). Liver enzymes (AST, ALT, GGT) and lipid parameters significantly decreased (all p < 0.001) except triglycerides (p = 0.001). FLI significantly decreased from baseline to 3 months (p < 0.001). Correlation analyses showed that ΔFLI was positively associated with Δweight (p < 0.001), ΔBMI (p < 0.001), ΔWC (p = 0.002), Δhs-CRP (p = 0.007), ΔHbA1c (p = 0.045), ΔAST (p = 0.026), and ΔHDL cholesterol (p = 0.023). Multiple regression analysis identified Δhs-CRP as the only independent predictor of ΔFLI (p = 0.007), explaining 29.8% of the variance. CONCLUSIONS: In a real-world setting, tirzepatide was associated with significant improvements in MASLD along with metabolic parameters and inflammation in obesity. Improvement in MASLD was independently associated with reduced low-grade inflammation. These findings support tirzepatide as a potential therapeutic option for MASLD management in the context of obesity.