Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists.

Agata Winiarska,Tomasz Stompór,Monika Knysak,Janusz Gumprecht,Katarzyna Nabrdalik

doi:10.3390/ijms221910822

Abstract

The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) agonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R agonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases.

Highlights

For the last two decades, the renal community has been mentally sliding into depression and nihilism
A recently published meta-analysis of four landmark cardio-vascular outcome trials on sodium-glucose cotransporter-2 inhibitors (SGLT2i) performed in patients with diabetes raised the possibility that this group of drugs may protect from stroke and that this effect may be most pronounced for canagliflozin when used in patients with advanced diabetic kidney disease (DKD)
The results demonstrating the impact of SGLT2i on cardio-vascular outcome in patients with heart failure and preserved ejection fraction regardless of diabetic status have been recently adopted by the recent European guidelines on heart failure in which empagliflozin and dapagliflozin gained the level of recommendation IA, regardless of diabetes [12]