Benefits of Sodium-Glucose Cotransporter-2 Inhibitors with Renin-Angiotensin System Blockers in Type-2 Diabetes: A Cohort Analysis

BACKGROUND Sodium-glucose cotransporter 2 inhibitors (SGLT2i) can benefit patients with type 2 diabetes mellitus by reducing hazardous renal outcomes. This study compared the renal benefits of combining SGLT2i with renin-angiotensin system blockers (RASB) versus combining RASB with dipeptidyl peptidase 4 inhibitors (DPP4i). MATERIAL AND METHODS This was a retrospective cohort study with a new-user and active-comparator design. The study utilized data from the Taiwan National Health Insurance Research Database, including patients with type 2 diabetes mellitus enrolled between January 1, 2016 and December 31, 2016. Participants were divided into 2 groups: the case group (n=3622) receiving RASB plus SGLT2i and the comparison group (n=3622) receiving RASB plus DPP4i. The groups were matched 1: 1 based on sex, age, and Charlson comorbidity index. Both groups were followed until December 31, 2020. Additionally, a global dataset of TriNetX was used for external validation. RESULTS After matching, unadjusted hazard ratios (HRs) showed significant differences favoring the SGLT2i group for chronic kidney disease (CKD) (HR: 0.66; 95% CI, 0.58-0.74), advanced kidney failure (HR: 0.64; 95% CI, 0.44-0.93), and initiation of long-term dialysis (HR: 0.61; 95% CI, 0.38-0.97). These differences remained significant after multivariable adjusting: CKD (HR: 0.74; 95% CI, 0.65-0.84), advanced kidney failure (HR: 0.62; 95% CI, 0.42-0.92), and commencement of long-term dialysis (HR: 0.53; 95% CI, 0.32-0.87). The renal benefits of the combination therapy were consistently observed in the TriNetX dataset. CONCLUSIONS This study shows the real-world benefits of combining SGLT2i with RASB, providing clinicians with valuable evidence to optimize renal outcomes in patients with type 2 diabetes.