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

Jul 5, 2025Hepatology research : the official journal of the Japan Society of Hepatology

Tirzepatide treatment and liver health markers in people with fatty liver disease and type 2 diabetes

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Abstract

Tirzepatide treatment led to significant improvements in body weight, liver enzymes, and hemoglobin A1c in patients with Type 2 diabetes and metabolic dysfunction-associated steatotic liver disease over 48 weeks.

Body weight, liver enzyme levels, and hemoglobin A1c showed significant reductions at Week 12, which were maintained throughout the treatment period.
Controlled attenuation parameter decreased significantly from baseline to 48 weeks.
Changes in body weight correlated with changes in alanine aminotransferase levels, indicating a relationship between weight loss and liver enzyme improvement.
Noninvasive tests for fibrosis demonstrated significant decreases in markers from baseline to 48 weeks.
Most adverse events were transient and mild, primarily gastrointestinal symptoms such as nausea, diarrhea, and constipation.

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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.

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

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