Renal and Hemodynamic Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Type 2 Diabetes and Chronic Kidney Disease Receiving Varying Doses of Renin-Angiotensin System Blockade

Renal and Hemodynamic Effects of SGLT2i

Abstract

Background: Chronic kidney disease (CKD) in the context of type 2 diabetes mellitus (T2DM) remains a significant global health challenge. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have emerged as a renoprotective therapy, often co-administered with renin–angiotensin system inhibitors (RASi). However, the clinical impact of background RASi intensity on SGLT2i-associated renal and hemodynamic outcomes remains unclear.
Methods: This retrospective study included 67 patients with T2DM and CKD initiated on SGLT2i therapy and followed for 12 months. Patients were stratified into three groups based on background RASi use: no RASi, moderate-dose RASi, and full-dose RASi. Clinical, biochemical, and hemodynamic parameters—including blood pressure, eGFR, proteinuria, and glycemic/metabolic markers—were evaluated at baseline, 3 months, and 12 months. Adverse events including acute kidney injury (AKI) and urinary tract infections (UTIs) were recorded.
Results: All groups exhibited significant reductions in systolic blood pressure (SBP), with the greatest decline observed in the full-dose RASi group (–13 mmHg at 12 months). A transient significant dip in eGFR was noted at month 3 in the full-dose group, with partial recovery by month 12. Proteinuria decreased significantly in both the moderate-dose and full-dose RASi groups, with the greatest absolute reduction in the moderate-dose group. Glycemic control improved across all groups, with the non-RASi group showing the most pronounced decline in fasting glucose and HbA1c. No significant differences in AKI or UTI incidence were observed among groups.
Conclusion: SGLT2i therapy is safe and effective across all RASi backgrounds. However, co-administration with RASi—particularly at full doses—appears to enhance antihypertensive, renal function, and antiproteinuric outcomes. These findings underscore the potential synergistic role of full-dose RAS blockade in optimizing the renoprotective benefits of SGLT2i in diabetic CKD.