Abstract
<title>Abstract</title> <p>Background While renin–angiotensin system inhibitors (RASi) are the standard of care for diabetic kidney disease (DKD), their long-term effectiveness in patients with type 2 diabetes mellitus (T2DM) across varying degrees of kidney function remains debated. Methods We conducted a retrospective, multicenter observational cohort study using a common data model (CDM) from three tertiary hospitals. We identified 18,707 patients with T2DM and stratified them into four cohorts: a DKD-free group and three groups with established chronic kidney disease (CKD) stages 3A, 3B, and 4. Using propensity score matching, we compared RASi users with active controls treated with other antihypertensives. The outcomes were major adverse cardiovascular events (MACEs) and major adverse kidney events (MAKEs). Random-effects meta-analyses were performed to pool incidence rate ratios (IRRs). Results In the DKD-free cohort, RASi use was not associated with a reduction in MACEs (IRR 1.079; 95% confidence interval [CI] 0.758–1.538) or MAKEs (IRR 1.014; 95% CI 0.646–1.592). In patients with established CKD, RASi use was associated with an increased risk of MAKEs: CKD stage 3A (IRR 1.429; 95% CI 1.324–1.542), stage 3B (IRR 1.346, 95% CI 1.090–1.663), and stage 4 (IRR 1.312; 95% CI 1.173–1.467). In the RASi groups, kidney events were more frequent, whereas in-hospital mortality was reduced or not significantly different across centers. Conclusion In this retrospective, real-world multicenter cohort, RASi therapy was not associated with improved kidney outcomes or a lower risk of MACEs in patients with T2DM, including those with advanced DKD. Given the concurrent signal toward preserved or reduced in-hospital mortality, these findings should inform individualized RASi decisions and close monitoring.</p>