Tahara Atsuo, Takasu Toshiyuki, Yokono Masanori, Imamura Masakazu, Kurosaki Eiji
Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
Eur J Pharmacol. 2017 Aug 15;809:163-171. doi: 10.1016/j.ejphar.2017.05.019. Epub 2017 May 12.
In this study, we investigated and compared the effects of all six sodium-glucose cotransporter (SGLT) 2 inhibitors commercially available in Japan on diabetes-related diseases and complications in type 2 diabetic mice. Following 4-week repeated administration to diabetic mice, all SGLT2 inhibitors showed significant improvement in diabetes-related diseases and complications, including obesity; abnormal lipid metabolism; steatohepatitis; inflammation; endothelial dysfunction; and nephropathy. While all SGLT2 inhibitors exerted comparable effects in reducing hyperglycemia, improvement of these diabetes-related diseases and complications was more potent with the two long-acting drugs (ipragliflozin and dapagliflozin) than with the four intermediate-acting four drugs (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin), albeit without statistical significance. These findings demonstrate that SGLT2 inhibitors alleviate various diabetic pathological conditions in type 2 diabetic mice, and suggest that SGLT2 inhibitors, particularly long-acting drugs, might be useful not only for hyperglycemia but also in diabetes-related diseases and complications, including nephropathy in type 2 diabetes.
在本研究中，我们调查并比较了日本市面上所有六种钠-葡萄糖协同转运蛋白（SGLT）2抑制剂对2型糖尿病小鼠糖尿病相关疾病及并发症的影响。对糖尿病小鼠进行4周重复给药后，所有SGLT2抑制剂均使糖尿病相关疾病及并发症有显著改善，包括肥胖、脂质代谢异常、脂肪性肝炎、炎症、内皮功能障碍及肾病。虽然所有SGLT2抑制剂在降低高血糖方面发挥了相当的作用，但两种长效药物（依帕列净和达格列净）在改善这些糖尿病相关疾病及并发症方面比四种中效药物（托格列净、卡格列净、恩格列净和鲁格列净）更有效，尽管无统计学意义。这些发现表明，SGLT2抑制剂可减轻2型糖尿病小鼠的各种糖尿病病理状况，并提示SGLT2抑制剂，尤其是长效药物，可能不仅对高血糖有效，而且对糖尿病相关疾病及并发症，包括2型糖尿病肾病也有用。
