Fukada Hiroo, Kon Kazuyoshi, Yaginuma Reiko, Uchiyama Akira, Morinaga Maki, Ishizuka Kei, Fukuhara Kyoko, Okubo Hironao, Suzuki Satoko, Nojiri Shuko, Yamashina Shunhei, Ikejima Kenichi
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan.
Front Med (Lausanne). 2025 Mar 25;12:1542741. doi: 10.3389/fmed.2025.1542741. eCollection 2025.
INTRODUCTION: Pharmacotherapy for metabolic dysfunction-associated steatotic liver disease (MASLD) is still under development and has not been fully established. For patients with MASLD and type 2 diabetes, treatment with antidiabetic drugs, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, is recommended, with vitamin E supplementation when treatment efficacy is insufficient. The benefits and risks of SGLT2 inhibitors for MASLD with type 2 diabetes have not been thoroughly investigated. OBJECTIVE: This prospective randomized controlled trial aimed to elucidate the effectiveness and risks of the SGLT2 inhibitor dapagliflozin in comparison with vitamin E in patients with MASLD and comorbid type 2 diabetes. METHODS: The trial enrolled 24 patients with MASLD and comorbid type 2 diabetes, who were assigned to receive either dapagliflozin (5 mg/day) or vitamin E (150 mg/day) for 24 weeks. The primary outcomes included serum levels of AST, ALT, γ-GT, and type IV collagen, and the FIB-4 index. The secondary outcomes were BMI, HbA1c and serum ferritin levels, lipid profile, body composition assessed using InBody, and hepatic fat content and fibrosis evaluated with FibroScan. Adverse events were monitored throughout the study period. RESULTS: Both groups demonstrated significant reductions in serum AST and ALT levels but intergroup differences were not significant. The dapagliflozin group showed additional benefits, with significant decreases in BMI and HbA1c, γ-GT, ferritin, LDL cholesterol, and body fat levels, indicating improved glycemic control and lipid profile. Dapagliflozin administration was associated with a significant decline in the skeletal muscle index, indicating a risk of muscle loss absent in the vitamin E group. This reduction in muscle mass is clinically significant as it suggests a potential risk of worsened overall survival with dapagliflozin treatment. CONCLUSION: This study indicates that dapagliflozin provides several metabolic benefits in patients with MASLD and comorbid type 2 diabetes, including reductions in the levels of liver enzymes and body fat, but the observed decrease in muscle mass suggests a potential adverse effect on long-term survival outcomes. Muscle mass should be monitored in patients receiving dapagliflozin therapy to mitigate the risk of sarcopenia progression and ensure a comprehensive approach to MASLD management. CLINICAL TRIAL REGISTRATION: https://jrct.niph.go.jp/re/reports/detail/81182, identifier jRCT1031180386.
引言：代谢功能障碍相关脂肪性肝病（MASLD）的药物治疗仍在发展中，尚未完全确立。对于患有MASLD和2型糖尿病的患者，建议使用抗糖尿病药物进行治疗，包括钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂，当治疗效果不足时补充维生素E。SGLT2抑制剂对合并2型糖尿病的MASLD的益处和风险尚未得到充分研究。 目的：这项前瞻性随机对照试验旨在阐明SGLT2抑制剂达格列净与维生素E相比，在患有MASLD合并2型糖尿病患者中的有效性和风险。 方法：该试验招募了24例患有MASLD合并2型糖尿病的患者，将他们分为两组，分别接受达格列净（5毫克/天）或维生素E（150毫克/天）治疗24周。主要结局指标包括血清AST、ALT、γ-GT和IV型胶原水平以及FIB-4指数。次要结局指标为BMI、糖化血红蛋白（HbA1c）和血清铁蛋白水平、血脂谱、使用InBody评估的身体成分，以及使用FibroScan评估的肝脂肪含量和纤维化程度。在整个研究期间监测不良事件。 结果：两组患者的血清AST和ALT水平均显著降低，但组间差异不显著。达格列净组显示出额外的益处，BMI、HbA1c、γ-GT、铁蛋白、低密度脂蛋白胆固醇和身体脂肪水平均显著降低，表明血糖控制和血脂谱得到改善。使用达格列净与骨骼肌指数显著下降相关，这表明维生素E组不存在肌肉流失风险。肌肉量的减少具有临床意义，因为这表明达格列净治疗可能存在总体生存率恶化的潜在风险。 结论：本研究表明，达格列净在患有MASLD合并2型糖尿病的患者中提供了多种代谢益处，包括降低肝酶水平和身体脂肪，但观察到的肌肉量减少表明对长期生存结局可能存在不良影响。在接受达格列净治疗的患者中应监测肌肉量，以减轻肌肉减少症进展的风险，并确保对MASLD进行全面管理。 临床试验注册：https://jrct.niph.go.jp/re/reports/detail/81182，标识符jRCT1031180386。
Front Med (Lausanne). 2023-12-11
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