Comparison of Tofogliflozin and Glimepiride Effects on Nonalcoholic Fatty Liver Disease in Participants With Type 2 Diabetes: A Randomized, 48-Week, Open-Label, Active-Controlled Trial.
Comparison of Tofogliflozin and Glimepiride Effects on Nonalcoholic Fatty Liver Disease in Participants With Type 2 Diabetes: A Randomized, 48-Week, Open-Label, Active-Controlled Trial.
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非酒精性脂肪性肝病（NAFLD）是2型糖尿病和肥胖的肝脏表型。目前，钠-葡萄糖协同转运蛋白2（SGLT 2）抑制剂和磺脲类药物在2型糖尿病伴NAFLD的肝脏病理学和肝脏基因表达谱中的疗效尚不清楚。我们进行了一项为期48周的随机、开放标签、平行组试验，涉及活检证实的NAFLD参与者。共有40名参与者被随机分配接受20 mg托福格列净或0.5 mg格列美脲每日一次治疗。主要结局是脂肪变性、肝细胞气球样变、小叶炎症和纤维化组织学分类的所有个体评分至少改善1分的参与者百分比。次要终点是肝酶、代谢标志物和肝脏基因表达谱的变化。托福格列净组的纤维化评分改善（60%，P = 0.001），而两组之间较基线的变化无显著差异（P = 0.172）。托格列净组的脂肪变性（65%，P = 0.001）、肝细胞气球样变性（55%，P = 0.002）和小叶炎症（50%，P = 0.003）等组织学变量得到改善，而格列美脲组仅肝细胞气球样变性得到改善（25%，P = 0.025）。肝脏基因表达谱显示了能量代谢、炎症和纤维化的组织学相关特征，这些特征可被托福格列净逆转。在患有2型糖尿病和NAFLD的参与者中，托福格列汀和格列美脲（在较小程度上）导致肝脏组织学和代谢改善，两种药物之间没有显著差异。参与能量代谢、炎症和纤维化的基因的肝脏表达与肝脏组织学变化密切相关，并被托福格列净挽救。我们需要通过SGLT 2抑制剂的长期大规模临床试验进一步证实。
Nonalcoholic fatty liver disease (NAFLD) is a liver phenotype of type 2 diabetes and obesity. Currently, the efficacy of sodium–glucose cotransporter 2 (SGLT2) inhibitors and sulfonylureas in liver pathology and hepatic gene expression profiles for type 2 diabetes with NAFLD are unknown. We conducted a 48 week, randomized, open-label, parallel-group trial involving participants with biopsy-confirmed NAFLD. A total of 40 participants were randomly assigned to receive once daily 20 mg tofogliflozin or 0.5 mg glimepiride. The primary outcome was the percentage of participants with at least an improvement in all individual scores for histological categories of steatosis, hepatocellular ballooning, lobular inflammation, and fibrosis by at least 1 point. The secondary end points were the changes in liver enzymes, metabolic markers, and hepatic gene expression profiles. Fibrosis scores improved in the tofogliflozin group (60%, P = 0.001), whereas the change from baseline did not differ significantly between the groups (P = 0.172). The histological variables of steatosis (65%, P = 0.001), hepatocellular ballooning (55%, P = 0.002), and lobular inflammation (50%, P = 0.003) were improved in the tofogliflozin group, whereas only hepatocellular ballooning was improved in the glimepiride group (25%, P = 0.025). Hepatic gene expression profiling revealed histology-associated signatures in energy metabolism, inflammation, and fibrosis that were reversed with tofogliflozin. Tofogliflozin and, to a lesser degree, glimepiride led to liver histological and metabolic improvement in participants with type 2 diabetes and NAFLD, with no significant difference between the agents. The hepatic expression of the genes involved in energy metabolism, inflammation, and fibrosis was well correlated with liver histological changes and rescued by tofogliflozin. We need further confirmation through long-term larger-scale clinical trials of SGLT2 inhibitors.
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影响因子：
5.8
作者：
Bolinder, Jan;Ljunggren, Osten;Parikh, Shamik
通讯作者：
Parikh, Shamik
DOI：
10.3803/enm.2018.33.3.387
发表时间：
2018-09
期刊：
Endocrinology and metabolism (Seoul, Korea)
影响因子：
--
作者：
Choi DH;Jung CH;Mok JO;Kim CH;Kang SK;Kim BY
通讯作者：
Kim BY
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
8.2
作者：
Eriksson JW;Lundkvist P;Jansson PA;Johansson L;Kvarnström M;Moris L;Miliotis T;Forsberg GB;Risérus U;Lind L;Oscarsson J
通讯作者：
Oscarsson J
影响因子：
16.2
作者：
Hamaguchi, Erika;Takamura, Toshinari;Kaneko, Shuichi
通讯作者：
Kaneko, Shuichi