Influence of SGLT2 Inhibitor Treatment on Urine Antioxidant Status in Type 2 Diabetic Patients: A Pilot Study

Abstract

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been recognized as potent antioxidant agents. Since SGLT2i are nephroprotective drugs, we aimed to examine the urine antioxidant status in patients with type 2 diabetes mellitus (T2DM). One hundred and one subjects participated in this study, including 37 T2DM patients treated with SGLT2i, 31 T2DM patients not using SGLT2i, and 33 healthy individuals serving as a control group. Total antioxidant capacity (TAC), superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD), free thiol groups (R-SH, sulfhydryl groups), and catalase (CAT) activity, as well as glucose concentration, were assessed in the urine of all participants. Urine SOD and MnSOD activity were significantly higher among T2DM patients treated with SGLT2i than T2DM patients without SGLT2i treatment ( p = 0.009 and p = 0.003 , respectively) and to the healthy controls ( p = 0.002 and p = 0.001 , respectively). TAC was significantly lower in patients with T2DM treated with SGLT2i when compared to those not treated and healthy subjects ( p = 0.036 and p = 0.019 , respectively). It could be hypothesized that the mechanism by which SGLT2i provides nephroprotective effects involves improvement of the SOD antioxidant activity. However, lower TAC might impose higher OS (oxidative stress), and elevation of SOD activity might be a compensatory mechanism.

An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

“…However, a meta-analysis of 15 randomized and 8 observational clinical studies of these drugs showed a consistent reduction in biomarkers of both inflammation (CRP, IL-6, and TNF-α) and oxidative stress (8-iso-prostaglandin F2α and 8-hydroxy-2′-deoxyguanosine) and an increase of the cardioprotective adiponectin derived from adipose tissue [ 257 ]. In a recent real-world observational pilot trial, treatment with various SGLT2-Is modified the redox status and antioxidant enzyme activity in the urine of T2DM patients [ 258 ].…”

Antioxidant Roles of SGLT2 Inhibitors in the Kidney

“…Contrarily, Nabrdalik-Leśniak et al have described that therapy of at least one month with either canagliflozin or empagliflozin decreased total antioxidant capacity (estimated by ABTS urine levels) in diabetic patients as compared to that of diabetic patients not treated with SGLT2is and healthy controls. However, the urinary activity of the antioxidant enzymes SOD and MnSOD was increased in diabetic patients treated with SGLT2is, suggesting that these drugs can also promote the activation of antioxidant mechanisms [ 100 ]. In this line, Iannantuoni et al have described that 24-week long treatment with empagliflozin reduces superoxide production, increases glutathione content (an antioxidant), and enhances the expression of glutathione s-reductase and catalase in leukocytes of diabetic patients.…”

Oxidative Stress Management in Cardiorenal Diseases: Focus on Novel Antidiabetic Agents, Finerenone, and Melatonin

“…Individuals on SGLT2 inhibitors alone exhibited only decreases in 2,2¢-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) radical after 12 months of follow-up, with no major differences being noted in the rest of the examined markers [ 88 ]. In another pilot study, SGLT2 inhibitors induced a reduction in urinary SOD and MnSOD activity, as well as in total antioxidant capacity, in individuals with type 2 diabetes mellitus [ 89 ]. The addition of SGLT2 inhibitors to angiotensin-converting enzyme inhibitor ramipril resulted in the lowering of urinary 8-isoprostane concentration compared to the addition of placebo to ramipril in the randomized, double-blind, placebo-controlled, crossover trial of Lytvyn et al [ 90 ].…”