SGLT2 Inhibitors for the Primary Prevention of CKD in Type 2 Diabetes: A Systematic Review and Meta-Analysis

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD), though their potential to prevent the development of CKD in type 2 diabetes needs to be examined. Purpose: Evaluate SGLT2 inhibitors for the primary prevention of CKD in people with type 2 diabetes. Data Sources: PubMed and Cochrane CENTRAL were searched through October 2025. Data Synthesis: Randomized controlled trials (RCTs) of SGLT2 inhibitors compared to placebo or other glucose-lowering agents in people with type 2 diabetes without baseline CKD were included. Outcomes were eGFR decline and incident albuminuria (i.e., UACR ≥30 mg/g). Random-effects meta-analyses were performed, and heterogeneity was assessed with I2. Certainty of evidence was evaluated with GRADE. PROSPERO CRD420251130722. Results: Eight RCTs were included: 5 cardiovascular outcomes trials comparing SGLT2 inhibitors and placebo (24072 participants) and 3 trials comparing SGLT2 inhibitors and sulfonylureas (2889 participants). Compared to placebo, SGLT2 inhibitors reduced the risk of incident albuminuria (3 trials, hazard ratio [HR]: 0.82, 95% CI (0.77-0.88), I2=0%, high certainty) and slowed eGFR decline based on chronic eGFR slope (5 trials, mean difference [MD]: 0.95 (0.84-1.07) ml/min/1.73 m2/year, I2=19%, high certainty) and total eGFR slope (4 trials, MD: 0.76 (0.50-1.03) ml/min/1.73 m2/year, I2=88%, moderate certainty). Compared to sulfonylureas, SGLT2 inhibitors slowed eGFR decline based on chronic eGFR slope (3 trials, MD: 2.43 (1.72-3.13) ml/min/1.73 m2/year, I2=55%, moderate certainty). Conclusions: In people with type 2 diabetes without CKD, SGLT2 inhibitors slow eGFR decline compared to both placebo and sulfonylureas and prevent incident albuminuria compared to placebo. Article Highlights (111/130 words) · Why did we undertake this study? To evaluate the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the primary prevention of chronic kidney disease (CKD) in people with type 2 diabetes. · What is the specific question(s) we wanted to answer? Can SGLT2 inhibitors prevent the onset of CKD in people with type 2 diabetes who do not have evidence of CKD at baseline? · What did we find? In people with type 2 diabetes without baseline CKD, SGLT2 inhibitors prevent incident albuminuria and slow eGFR decline. · What are the implications of our findings? Evidence supports the use of SGLT2 inhibitors for the primary prevention of CKD in people with type 2 diabetes.