| Autor: |
Yuval Ishay, Joel Neutel, Yotam Kolben, Ram Gelman, Orly Sneh Arbib, Oliver Lopez, Helena Katchman, Rizwana Mohseni, Miriam Kidron, Yaron Ilan |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Gastro Hep Advances, Vol 3, Iss 3, Pp 417-425 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2772-5723 |
| DOI: |
10.1016/j.gastha.2023.11.016 |
| Popis: |
Background and Aims: Metabolic dysfunction-associated steatohepatitis is an advanced form of nonalcoholic fatty liver disease and a leading cause of end-stage liver disease and transplantation. Insulin resistance and inflammation underlie the pathogenesis of the disease. Methods: This double-blind, randomized, placebo-controlled, multicenter feasibility clinical trial aimed to determine the safety of oral 8 mg insulin in patients with metabolic dysfunction-associated steatohepatitis and type 2 diabetes mellitus. Patients were treated twice daily for 12 weeks with an 8 mg insulin (n = 21) or placebo (n = 11) capsule. Safety was monitored throughout the study. MRI-proton density fat fraction assessed liver fat content, and Fibroscan® measured liver fibrosis and steatosis levels at screening and after 12 weeks of treatment. Results: No severe drug-related adverse events were reported during the study. After 12 weeks of treatment, mean percent reductions in whole-liver (−11.2% vs −6.5%, respectively) and liver segment 3 (−11.7% vs +0.1%, respectively) fat content was higher in the insulin than in the placebo arm. Patients receiving insulin showed a median −1.2 kPa and −21.0 dB/m reduction from baseline fibrosis and steatosis levels, respectively, while placebo-treated patients showed median increases of 0.3 kPa and 13.0 dB/m, respectively. At Week 12, oral insulin was associated with a mean of 0.27% reduction and placebo with a 0.23% increase from baseline hemoglobin A1c levels. Mean percent changes from baseline alanine aminotransferase, and aspartate aminotransferase levels were −10% and −0.8%, respectively, in the oral insulin and 3.0% and 13.4%, in the placebo arm. Conclusion: The results of this feasibility study support the safety and potential therapeutic effect of orally delivered insulin on liver fibrosis, fat accumulation, and inflammatory processes (NIH Clinical Trials No. NCT04618744). |
| Databáze: |
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