Effect of Tirzepatide Treatment on Hepatic Biomarkers in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes Mellitus.

AIM: This study aimed to clarify the impact of tirzepatide as a treatment for Type 2 diabetes mellitus (T2DM) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This single-arm, prospective, observational pilot study included 16 patients with MASLD and T2DM who were treated with tirzepatide. Of these, 13 patients completed 48 weeks of treatment. Tirzepatide was initiated at a dose of 2.5 mg once weekly for 4 weeks, and dose adjustments were left to the discretion of the attending physician based on efficacy and adverse events. RESULTS: Significant improvements in body weight, liver enzymes, and hemoglobin A1c were found at Week 12 and were sustained throughout the 48-week treatment period compared with baseline values (all p < 0.05). Controlled attenuation parameter significantly decreased from baseline to 48 weeks (p < 0.05). Changes in body weight were correlated with changes in alanine aminotransferase levels (r = 0.57, p < 0.05) but not with changes in controlled attenuation parameter (r = 0.45, p = 0.12). The results of noninvasive tests for fibrosis, including Type IV collagen 7s, Wisteria floribunda agglutinin-positive Mac-2-binding protein, the fibrosis-4 index, and the liver stiffness measurement, significantly decreased from baseline to 48 weeks (all p < 0.05). Most adverse events were transient Grades 1-2 gastrointestinal symptoms, including nausea (5 patients, 31.3%), diarrhea (3 patients, 18.8%), and constipation (2 patients, 12.5%). CONCLUSIONS: Tirzepatide treatment for T2DM in patients with MASLD significantly improved liver steatosis and injury, surrogate markers of liver fibrosis, and diabetes status, and reduced body weight.