期刊
PHARMACOLOGY & THERAPEUTICS
卷 249, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2023.108503
关键词
Diabetes; Kidney; Diabetic nephropathy; SGLT2 inhibitor
A systematic review of studies on SGLT2 inhibitors in rodent models of diabetes showed that these inhibitors not only improved glycemic control but also had various beneficial effects on renal function. These nephroprotective effects were observed in different animal models of type 1 and type 2 diabetes/obesity. SGLT2 inhibitors had positive effects on lipid metabolism, blood pressure, glomerulosclerosis, renal tubular fibrosis, apoptosis, oxidative stress, and inflammation, which are important pathomechanisms for atherosclerosis and renal health. However, more data on female animals and direct comparative studies with other anti-diabetic compounds are needed.
We have performed a systematic review of studies reporting on the renal effects of SGLT2 inhibitors in rodent models of diabetes. In 105 studies, SGLT2 inhibitors improved not only the glycemic control but also various aspects of renal function in most cases. These nephroprotective effects were similarly reported whether treatment with the SGLT2 inhibitor started concomitant with the onset of diabetes (within 1 week), early after onset (1-4 weeks) or after nephropathy had developed (>4 weeks after onset) with the latter probably having the greatest translational value. They were observed across various animal models of type 1 and type 2 diabetes/obesity (4 and 23 models, respectively), although studies in the type 2 diabetes model of db/db mice more often had negative data than in other models. Among possibly underlying pathophysiological mechanisms of nephroprotection, treatment with SGLT2 inhibitors had beneficial effects on lipid metabolism, blood pressure, glomerulosclerosis as well as renal tubular fibrosis, apoptosis, oxidative stress, and inflammation. These pathomechanisms highly influence atherosclerosis and renal health, which are two major factors that lead to an enhanced mortality in patients with diabetes and/or chronic kidney disease. Interestingly, renal SGLT2 inhibitor effects did not always correlate with those on glucose homeostasis, particularly in a limited number of direct comparative studies with other anti-diabetic treatments, indicating that nephroprotection may at least partly occur by mechanisms other than improving glycemic control. Our analyses did not provide evidence for different nephroprotective efficacy between SGLT2 inhibitors. Importantly, only four of 105 studies reported on female animals, and none provided direct comparative data between sexes. We conclude that more data on female animals and more direct comparative studies with other anti-diabetic compounds and combinations of treatments are needed.& COPY; 2023 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据