Frederik Persson1, Peter Rossing2,3, Priya Vart4, Glenn M Chertow5, Fan Fan Hou6, Niels Jongs4, John J V McMurray7, Ricardo Correa-Rotter8, Harpreet S Bajaj9, Bergur V Stefansson10, Robert D Toto11, Anna Maria Langkilde10, David C Wheeler12,13, Hiddo J L Heerspink. 1. Steno Diabetes Center Copenhagen, Gentofte, Denmark frederik.persson@regionh.dk. 2. Steno Diabetes Center Copenhagen, Gentofte, Denmark. 3. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 4. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands. 5. Departments of Medicine and Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA. 6. Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China. 7. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K. 8. National Medical Science and Nutrition Institute Salvador Zubirán, Mexico City, Mexico. 9. LMC Diabetes and Endocrinology, Brampton, Ontario, Canada. 10. Late-stage Development, Cardiovascular, Renal and Metabolism, Biopharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden. 11. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX. 12. Department of Renal Medicine, University College London, London, U.K. 13. The George Institute for Global Health, Sydney, Australia.
Abstract
OBJECTIVE: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status. RESEARCH DESIGN AND METHODS: We enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2, and urinary albumin-to-creatinine ratio 200-5,000 mg/g. The primary composite end point was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. RESULTS:Of 4,304 participants, 738 had normoglycemia, 660 had prediabetes, and 2,906 had type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (P for interaction = 0.19) in normoglycemia (hazard ratio [HR] 0.62 [95% CI 0.39, 1.01]), prediabetes (HR 0.37 [0.21, 0.66]), and type 2 diabetes (HR 0.64 [0.52, 0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes. CONCLUSIONS:Dapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status.
RCT Entities:
OBJECTIVE: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status. RESEARCH DESIGN AND METHODS: We enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2, and urinary albumin-to-creatinine ratio 200-5,000 mg/g. The primary composite end point was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. RESULTS: Of 4,304 participants, 738 had normoglycemia, 660 had prediabetes, and 2,906 had type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (P for interaction = 0.19) in normoglycemia (hazard ratio [HR] 0.62 [95% CI 0.39, 1.01]), prediabetes (HR 0.37 [0.21, 0.66]), and type 2 diabetes (HR 0.64 [0.52, 0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes. CONCLUSIONS:Dapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status.
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