Abstract

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors provide renal and cardiovascular benefits in diabetes, but their effects in non-diabetic populations remain unclear. This meta-analysis evaluates the renal outcomes of SGLT2 inhibitors vs. placebo, focusing on diabetes status, subgroup variations, and drug-specific effects.
Materials and methods: A systematic review of 31 randomized controlled trials (RCTs) (98,516 patients) was conducted. Studies including diabetic and non-diabetic patients were analyzed, with subgroup assessments based on diabetes status, drug type, dose, baseline estimated glomerular filtration rate (eGFR), chronic kidney disease (CKD) stage, and follow-up duration. Primary outcomes included kidney disease progression, while secondary outcomes encompassed renal adverse events, composite renal outcomes, acute kidney injury (AKI), diabetic ketoacidosis (DKA), and renal failure.
Results: SGLT2 inhibitors reduced progressive kidney disease risk in diabetic (OR = 0.64, 95% CI: 0.58 – 0.71) and non-diabetic patients (OR = 0.69, 95% CI: 0.57 – 0.83), with no effect modification by diabetes status (p = 0.49). Among diabetics, risk reductions were notable for canagliflozin 100 mg, dapagliflozin 10 mg, and empagliflozin 10-mg, particularly in patients with CKD stage 2 – 3 and baseline eGFR of 30 – 90 mL/min/1.73m². Among non-diabetics, dapagliflozin and empagliflozin showed consistent benefit. No differences in renal adverse events were observed in either group. DKA risk was elevated in diabetics receiving SGLT2 inhibitors (OR = 2.18, 95% CI: 1.61 – 2.97), particularly with ertugliflozin, sotagliflozin, and dapagliflozin.
Conclusion: SGLT2 inhibitors confer renal protection in both diabetic and non-diabetic populations, supporting their use in CKD management across a broad spectrum of patients. However, careful drug selection is warranted in diabetic patients at risk for DKA.

Author Details

Authors

• Jingfeng Qian
• Yanqiu Xu

Departments

• Department of Nephrology, Yueyang Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China

Address

Jingfeng Qian
Department of Nephrology
Yueyang Hospital of Integrative Medicine
Shanghai University of Traditional Chinese Medicine
Shanghai, China
Email: [email protected]

Citation