RAAS Inhibitors for the Primary Prevention of CKD in Type 1 and Type 2 Diabetes: A Systematic Review and Meta-analysis

BACKGROUND The benefits of renin-angiotensin-aldosterone system (RAAS) inhibitors in people with diabetes and chronic kidney disease (CKD) are well established, although their effects in people with diabetes without CKD have yet to be fully characterized. PURPOSE This study evaluated the effects of RAAS inhibitors on the development of CKD in people with diabetes without CKD. DATA SOURCES Searches were conducted in PubMed and Cochrane CENTRAL from inception through October 2025. STUDY SELECTION Eligible studies were randomized controlled trials (RCTs) of RAAS inhibitors versus placebo in people with type 1 or type 2 diabetes without baseline CKD. Outcomes were incident albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g) and estimated glomerular filtration rate (eGFR) decline (eGFR <60 mL/min/1.73 m2, slopes, and mean change). DATA SYNTHESIS Random-effects meta-analyses were conducted separately for type 1 and type 2 diabetes, and heterogeneity was assessed using I2. Certainty of evidence was assessed following the GRADE approach. RESULTS Fifteen RCTs were identified, nine for type 2 diabetes (majority of participants had hypertension) and six for type 1 diabetes (all participants were normotensive). RAAS inhibitors reduced the risk of incident albuminuria in type 2 diabetes (18,938 participants; risk ratio [RR] 0.83 [95% CI 0.76–0.91]; I2 = 13%; high certainty) but not in type 1 diabetes (4,047 participants; RR 0.98 [95% CI 0.66–1.47]; I2 = 50%; moderate certainty). Evidence on eGFR decline was limited, with no clear effects in type 1 or type 2 diabetes. CONCLUSIONS RAAS inhibitors prevent incident albuminuria in people with type 2 diabetes and hypertension, although effects on eGFR are unclear. No benefits were observed in people with type 1 diabetes and normotension.