Perkovic, VladoJardine, Meg JNeal, BruceBompoint, SeverineHeerspink, Hiddo J LCharytan, David MEdwards, RobertAgarwal, RajivBakris, GeorgeBull, ScottCannon, Christopher PCapuano, GeorgeChu, Pei-Lingde Zeeuw, DickGreene, TomLevin, AdeeraPollock, CarolWheeler, David CYavin, YshaiZhang, HongZinman, BernardMeininger, GaryBrenner, Barry MMahaffey, Kenneth WCREDENCE Trial Investigators2025-01-072025-01-072019-04-14https://hdl.handle.net/10668/26680Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P = 0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.).enAgedCanagliflozinCardiovascular DiseasesCreatinineDiabetes Mellitus, Type 2Diabetic NephropathiesDouble-Blind MethodFemaleFollow-Up StudiesGlomerular Filtration RateHumansKidney Failure, ChronicMaleMiddle AgedSodium-Glucose Transporter 2 Inhibitorsresearch article30990260open access10.1056/NEJMoa18117441533-4406https://www.nejm.org/doi/pdf/10.1056/NEJMoa1811744?articleTools=true