Renal outcomes of combination therapy with sodium-glucose cotransporter 2 inhibitors plus renin-angiotensin system blockers in patients with type 2 diabetes mellitus: A population-based cohort study

Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) can benefit patients with type 2 diabetes mellitus by reducing hazardous renal outcomes. This study aimed to evaluate whether the combination of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and conventional renin-angiotensin system blockers (RASB) provides a synergistic effect on renal outcomes in patients with type 2 diabetes mellitus, compared to the combination of RASB and dipeptidyl peptidase 4 inhibitors (DPP4i). Methods This is a retrospective cohort study. The study utilized data from the Taiwan National Health Insurance Research Database (NHIRD), including patients with type 2 diabetes mellitus enrolled between January 1, 2016, and December 31, 2016. Participants were divided into two groups: the case group (n = 3,622) receiving RASB plus SGLT2i and the comparison group (n = 3,622) receiving RASB plus DPP4i. The groups were matched 1:1 based on gender, age, and Charlson comorbidity index. Additionally, TriNetX was used for external validation. Results Prior to 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 post-matching: 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. Limitations NHIRD lacks key clinical factors (e.g., physical features, lab data), potential baseline disparities due to retrospective design, and limited generalizability beyond Taiwanese patients, despite TriNexT validation. Conclusions In patients with type 2 diabetes mellitus, combination therapy with SGLT2i and RASB yielded better renal outcomes.