Effects of Empagliflozin/Linagliptin on Oxidative Stress Markers in Patients with Chronic Kidney Disease and Type 2 Diabetes: A Randomized, Open-Label, Controlled Trial
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Abstract
Background: Combined therapies using sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) are expected to yield additive effects on glycemic control and reactive oxygen species (ROS) among patients with type 2 diabetes (T2DM). This study evaluated whether SGLT2i and DPP-4i could attenuate renal oxidative stress caused by chronic hyperglycemia.
Methods: A clinical trial was conducted among patients with T2DM and stage 3 chronic kidney disease (CKD). Patients were randomized 1:1 to receive either empagliflozin (10 mg/day)/linagliptin (5 mg/day) or standard treatment for 12 weeks. Renal oxidative stress and renal biomarkers were measured using urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) and the urine albumin-to-creatinine ratio.
Results: Forty-eight patients were analyzed. At week 12, the empagliflozin/linagliptin group showed a significant reduction in urinary 8-OHdG compared with the control group. Additionally, the empagliflozin/linagliptin group had a significant reduction in urinary albumin compared with the control group. The reduction in HbA1c with empagliflozin/linagliptin treatment was also superior to that observed with the control treatment. No between-group differences were observed regarding body weight, blood pressure, or estimated glomerular filtration rate at the end of follow-up. The proportion of subjects experiencing adverse events over 12 weeks was similar across treatment arms, with no hypoglycemic events requiring assistance.
Conclusions: Combined SGLT2i and DPP-4i treatment for 12 weeks improved renal oxidative stress and glycemic control in patients with T2DM and CKD. The treatment was well-tolerated.
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