PF-04971729

Ertugliflozin（CAS 号 1210344-57-2）是一种高选择性钠 - 葡萄糖协同转运蛋白 2（SGLT2）抑制剂（对 SGLT2 的选择性较 SGLT1 高 2000 倍以上），核心生物学功能包括降低 2 型糖尿病（T2D）患者血糖、减轻体重，发挥心血管保护（降低心衰住院风险）、肾脏保护作用，同时在溃疡性结肠炎（UC）模型中具有抗炎、黏膜修复活性，作用类型为特异性抑制 SGLT2 介导的肾脏葡萄糖重吸收；常用于用于疾病模型治疗，常见模型包括乙酸诱导的 UC 大鼠模型、心脏压力超负荷模型及 T2D 相关模型（如高脂饮食诱导糖尿病模型），分别用于评估抗炎黏膜修复、心血管保护及降糖减重效果。

常用应用与浓度：动物实验中，UC 模型口服 1、5、10 mg/kg/ 天（10 mg/kg 剂量疗效与柳氮磺吡啶 100 mg/kg 相当），心脏模型相关给药浓度未明确；临床中 T2D 患者常用剂量为 5 mg 或 15 mg 每日一次口服，可作为单药或添加治疗，合并动脉粥样硬化性心血管疾病的 T2D 患者同样适用；有效治疗浓度：临床中 5 mg 和 15 mg 每日一次可显著降低糖化血红蛋白、减轻体重（VERTIS FACTORIAL 研究中 15 mg 组减重 3.7 kg，占初始体重 4.2%），15 mg 剂量在体重降低方面效果更优，且能降低心衰住院风险（ hazard ratio 0.70，95% CI 0.54-0.90）；动物实验中 10 mg/kg 口服可抑制 UC 模型的 NF-κB 信号通路、下调 miR-155 表达，促进 M2 巨噬细胞极化，修复肠道黏膜屏障，改善心脏压力超负荷模型的心肌重构；安全性方面，可能增加骨折风险（RR 2.47，无统计学显著差异），无严重不良反应相关明确浓度关联数据。

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