Abstract
The utilization of sodium-glucose cotransporter-2 (SGLT2) inhibitors for kidney ailments has been a story of unexpected developments. The initial study by Rossetti and colleagues in 1987 proposed the idea of blocking SGLTs in the renal tubules to stimulate glucosuria. The development of orally absorbed SGLT2 inhibitors in the 1990s resulted in numerous trials, including cardiovascular outcomes trials (CVOTs) that demonstrated the benefits of SGLT2 inhibitors in protecting against secondary kidney disease endpoints. Trials with kidney disease endpoints as primary outcomes further verified these benefits. These trials found that SGLT2 inhibitors were superior to placebo, with a relative risk reduction of 40% for kidney disease progression in patients with or without type 2 diabetes. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, the DAPA-CKD trial, and the EMPA-KIDNEY trial all demonstrated the efficacy of SGLT2 inhibitors in reducing the progression of kidney disease, leading to a significant reduction in the relative risk of end-stage kidney disease, acute myocardial infarction, stroke, or cardiovascular death.
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