SGLT2 Inhibitors for the Primary Prevention of CKD in Type 2 Diabetes: A Systematic Review and Meta-analysis
Raveendhara R. Bannuru, Katherine Fazioli, Nicole M. Bhave, Ian H. de Boer, Amy Earley, Nuha A. ElSayed, Kamlesh Khunti, Sankar D. Navaneethan, Joshua J. Neumiller, Meredith Noble, Caroline Richardson, Peter Rossing, Shylaja Srinivasan, Katherine R. Tuttle, Deborah J. Wexler, Sylvia E. Rosas, Paola FiorettoBACKGROUND
Sodium–glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD), although their potential to prevent the development of CKD in type 2 diabetes needs to be examined.
PURPOSE
To evaluate SGLT2 inhibitors for the primary prevention of CKD in people with type 2 diabetes.
DATA SOURCES
PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) were searched through October 2025.
DATA SYNTHESIS
Randomized controlled trials (RCTs) of SGLT2 inhibitors compared with placebo or other glucose-lowering agents in people with type 2 diabetes without baseline CKD were included. Outcomes were estimated glomerular filtration rate (eGFR) decline and incident albuminuria (i.e., urine albumin-to-creatine ratio [UACR] ≥30 mg/g). Random-effects meta-analyses were performed, and heterogeneity was assessed with I2. Certainty of evidence was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
Eight RCTs were included: five cardiovascular outcomes trials comparing SGLT2 inhibitors and placebo (24,072 participants) and three trials comparing SGLT2 inhibitors and sulfonylureas (2,889 participants). Compared with placebo, SGLT2 inhibitors reduced the risk of incident albuminuria (three trials; hazard ratio 0.82; 95% CI 0.77–0.88; I2 = 0%, high certainty) and slowed eGFR decline based on the chronic eGFR slope (five trials; mean difference [MD] 0.95 [95% CI 0.84–1.07] mL/min/1.73 m2/year; I2 = 19%, high certainty) and total eGFR slope (four trials; MD 0.76 [0.50–1.03] mL/min/1.73 m2/year; I2 = 88%, moderate certainty). Compared with sulfonylureas, SGLT2 inhibitors slowed eGFR decline based on the chronic eGFR slope (three 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 with both placebo and sulfonylureas and prevent incident albuminuria compared with placebo.