A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease

Summary

The purpose of this study is to evaluate the effect of dapagliflozin on renal outcomes and cardiovascular mortality in patients with chronic kidney disease.

Timeline

Start

2017-02-02

Primary completion

2020-06-12

Completion

2020-06-12

Publications

• Moedt E, Koshino A, Jongs N, Ju W, Nair V, Kretzler M, Hansen MK, Arnott CG, Wheeler DC, Rossing P, Coca SG, Hammarstedt A, Greasley PJ, Bjornstad P, Bakker SJL, Heerspink HJL. Association of Urinary EGF with Kidney Outcomes and Effects of Sodium-Glucose Cotransporter 2 Inhibition. J Am Soc Nephrol. 2026 Apr 2. doi: 10.1681/ASN.0000001086. Online ahead of print.
• Heerspink HJL, Chertow GM, Rossing P, Correa-Rotter R, Sjostrom CD, Toto RD, Wheeler DC, Jongs N. Effects of Dapagliflozin on Progression of CKD According to Different Rates of Pretrial eGFR Loss. Clin J Am Soc Nephrol. 2025 Nov 1;20(11):1527-1535. doi: 10.2215/CJN.0000000810. Epub 2025 Sep 9.
• Bakker WM, Heerspink HJL, Jongs N, Correa-Rotter R, Rossing P, Toto RD, Wheeler DC, McMurray JJV, Langkilde AM, Gansevoort RT, Chertow GM, Vart P. Effects of Dapagliflozin on Health-Related Quality of Life in Patients with CKD. J Am Soc Nephrol. 2026 Jan 1;37(1):101-109. doi: 10.1681/ASN.0000000776. Epub 2025 Jul 18.
• Oshima M, Buizen L, Jongs N, Levin A, Chertow GM, Wheeler DC, Heerspink HJL, Arnott C, Jardine MJ, Mahaffey KW, Pollock C, Herrington WG, Perkovic V, Neuen BL. Sodium-Glucose Cotransporter 2 Inhibition and Hospitalizations in Patients with CKD: A Meta-Analysis of Kidney Outcome Trials. Clin J Am Soc Nephrol. 2025 Jul 14;20(9):1206-1214. doi: 10.2215/CJN.0000000771.
• Jongs N, Gasparyan SB, Frison L, Schloemer P, Brinker M, Little DJ, Heerspink HJL. Use of eGFR Slope Thresholds as End Point Components in a Kidney Disease Progression Hierarchical Composite End Point. J Am Soc Nephrol. 2025 Dec 1;36(12):2421-2430. doi: 10.1681/ASN.0000000766. Epub 2025 Jun 17.
• van Mil D, Vart P, Chertow GM, Gansevoort RT, Rossing P, Toto RD, Correa-Rotter R, Langkilde AM, Sjostrom CD, Wheeler DC, Heerspink HJL. Baseline, Early Changes, and Residual Albuminuria: Post Hoc Analysis of a Randomized Clinical Trial of Dapagliflozin in Chronic Kidney Disease. Clin J Am Soc Nephrol. 2024 Dec 1;19(12):1574-1584. doi: 10.2215/CJN.0000000000000550.
• Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.
• Fletcher RA, Herrington WG, Agarwal R, Mayne KJ, Arnott C, Jardine MJ, Mahaffey KW, Perkovic V, Staplin N, Wheeler DC, Chertow GM, Heerspink HJL, Neuen BL. Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cause-Specific Cardiovascular Death in Patients with CKD: A Meta-Analysis of CKD Progression Trials. Clin J Am Soc Nephrol. 2024 Sep 1;19(9):1180-1182. doi: 10.2215/CJN.0000000000000470. Epub 2024 Apr 16.
• Zhang Z, Heerspink HJL, Chertow GM, Correa-Rotter R, Gasparrini A, Jongs N, Langkilde AM, McMurray JJV, Mistry MN, Rossing P, Toto RD, Vart P, Nitsch D, Wheeler DC, Caplin B. Ambient heat exposure and kidney function in patients with chronic kidney disease: a post-hoc analysis of the DAPA-CKD trial. Lancet Planet Health. 2024 Apr;8(4):e225-e233. doi: 10.1016/S2542-5196(24)00026-3.
• Heerspink HJL, Stack AG, Terkeltaub R, Jongs N, Inker LA, Bjursell M, Maklad N, Perl S, Eklund O, Rikte T, Sjostrom CD, Perkovic V; SAPPHIRE Investigators. Combination Treatment with Verinurad and Allopurinol in CKD: A Randomized Placebo and Active Controlled Trial. J Am Soc Nephrol. 2024 May 1;35(5):594-606. doi: 10.1681/ASN.0000000000000326. Epub 2024 Feb 20.
• Koshino A, Schechter M, Chertow GM, Vart P, Jongs N, Toto RD, Rossing P, Correa-Rotter R, McMurray JJV, Gorriz JL, Isidto R, Kashihara N, Langkilde AM, Wheeler DC, Heerspink HJL. Dapagliflozin and Anemia in Patients with Chronic Kidney Disease. NEJM Evid. 2023 Jun;2(6):EVIDoa2300049. doi: 10.1056/EVIDoa2300049. Epub 2023 May 19.
• Yu MK, Vart P, Jongs N, Correa-Rotter R, Rossing P, McMurray JJV, Hou FF, Douthat W, Khullar D, Langkilde AM, Wheeler DC, Heerspink HJL, Chertow GM. Effects of Dapagliflozin in Chronic Kidney Disease Across the Spectrum of Age and by Sex. J Gen Intern Med. 2024 May;39(6):921-930. doi: 10.1007/s11606-023-08397-9. Epub 2023 Dec 14.
• Fletcher RA, Jongs N, Chertow GM, McMurray JJV, Arnott C, Jardine MJ, Mahaffey KW, Perkovic V, Rockenschaub P, Rossing P, Correa-Rotter R, Toto RD, Vaduganathan M, Wheeler DC, Heerspink HJL, Neuen BL. Effect of SGLT2 Inhibitors on Discontinuation of Renin-angiotensin System Blockade: A Joint Analysis of the CREDENCE and DAPA-CKD Trials. J Am Soc Nephrol. 2023 Dec 1;34(12):1965-1975. doi: 10.1681/ASN.0000000000000248. Epub 2023 Oct 25.
• Heerspink HJL, Jongs N, Schloemer P, Little DJ, Brinker M, Tasto C, Karpefors M, Wheeler DC, Bakris G, Perkovic V, Nkulikiyinka R, Rossert J, Gasparyan SB. Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression. J Am Soc Nephrol. 2023 Dec 1;34(12):2025-2038. doi: 10.1681/ASN.0000000000000243. Epub 2023 Oct 24.
• Chertow GM, Correa-Rotter R, Vart P, Jongs N, McMurray JJV, Rossing P, Langkilde AM, Sjostrom CD, Toto RD, Wheeler DC, Heerspink HJL; DAPA-CKD Trial Committees and Investigators. Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA-CKD Trial. J Am Heart Assoc. 2023 May 2;12(9):e028739. doi: 10.1161/JAHA.122.028739. Epub 2023 Apr 29.
• Vart P, Jongs N, Wheeler DC, Heerspink HJL, Langkilde AM, Chertow GM. Effectiveness and Safety of Dapagliflozin for Black vs White Patients With Chronic Kidney Disease in North and South America: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 Apr 3;6(4):e2310877. doi: 10.1001/jamanetworkopen.2023.10877.
• Willigers BJA, Ouwens M, Briggs A, Heerspink HJL, Pollock C, Pecoits-Filho R, Tangri N, Kovesdy CP, Wheeler DC, Garcia Sanchez JJ. The Role of Expert Opinion in Projecting Long-Term Survival Outcomes Beyond the Horizon of a Clinical Trial. Adv Ther. 2023 Jun;40(6):2741-2751. doi: 10.1007/s12325-023-02503-3. Epub 2023 Apr 18.
• Schechter M, Jongs N, Chertow GM, Mosenzon O, McMurray JJV, Correa-Rotter R, Rossing P, Langkilde AM, Sjostrom CD, Toto RD, Wheeler DC, Heerspink HJL. Effects of Dapagliflozin on Hospitalizations in Patients With Chronic Kidney Disease : A Post Hoc Analysis of DAPA-CKD. Ann Intern Med. 2023 Jan;176(1):59-66. doi: 10.7326/M22-2115. Epub 2022 Dec 6.
• Vart P, Vaduganathan M, Jongs N, Remuzzi G, Wheeler DC, Hou FF, McCausland F, Chertow GM, Heerspink HJL. Estimated Lifetime Benefit of Combined RAAS and SGLT2 Inhibitor Therapy in Patients with Albuminuric CKD without Diabetes. Clin J Am Soc Nephrol. 2022 Dec;17(12):1754-1762. doi: 10.2215/CJN.08900722. Epub 2022 Nov 22.
• McEwan P, Darlington O, Miller R, McMurray JJV, Wheeler DC, Heerspink HJL, Briggs A, Bergenheim K, Garcia Sanchez JJ. Cost-Effectiveness of Dapagliflozin as a Treatment for Chronic Kidney Disease: A Health-Economic Analysis of DAPA-CKD. Clin J Am Soc Nephrol. 2022 Dec;17(12):1730-1741. doi: 10.2215/CJN.03790322. Epub 2022 Nov 2.
• Jongs N, Chertow GM, Greene T, McMurray JJV, Langkilde AM, Correa-Rotter R, Kashihara N, Rossing P, Sjostrom CD, Stefansson BV, Toto RD, Wheeler DC, Heerspink HJL; DAPA-CKD Trial Committees and Investigators; Members of the DAPA-CKD Trial Committees and Investigators. Correlates and Consequences of an Acute Change in eGFR in Response to the SGLT2 Inhibitor Dapagliflozin in Patients with CKD. J Am Soc Nephrol. 2022 Nov;33(11):2094-2107. doi: 10.1681/ASN.2022030306. Epub 2022 Aug 17.
• Vart P, Correa-Rotter R, Hou FF, Jongs N, Chertow GM, Langkilde AM, McMurray JJV, Rossing P, Sjostrom CD, Stefansson BV, Toto RD, Douthat W, Escudero E, Isidto R, Khullar D, Bajaj HS, Wheeler DC, Heerspink HJL. Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions. Kidney Int Rep. 2022 Feb 2;7(4):699-707. doi: 10.1016/j.ekir.2022.01.1060. eCollection 2022 Apr.
• Waijer SW, Vart P, Cherney DZI, Chertow GM, Jongs N, Langkilde AM, Mann JFE, Mosenzon O, McMurray JJV, Rossing P, Correa-Rotter R, Stefansson BV, Toto RD, Wheeler DC, Heerspink HJL. Effect of dapagliflozin on kidney and cardiovascular outcomes by baseline KDIGO risk categories: a post hoc analysis of the DAPA-CKD trial. Diabetologia. 2022 Jul;65(7):1085-1097. doi: 10.1007/s00125-022-05694-6. Epub 2022 Apr 21.
• Heerspink HJL, Jongs N, Chertow GM, Langkilde AM, McMurray JJV, Correa-Rotter R, Rossing P, Sjostrom CD, Stefansson BV, Toto RD, Wheeler DC, Greene T; DAPA-CKD Trial Committees and Investigators. Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021 Nov;9(11):743-754. doi: 10.1016/S2213-8587(21)00242-4. Epub 2021 Oct 4.
• Jongs N, Greene T, Chertow GM, McMurray JJV, Langkilde AM, Correa-Rotter R, Rossing P, Sjostrom CD, Stefansson BV, Toto RD, Wheeler DC, Heerspink HJL; DAPA-CKD Trial Committees and Investigators. Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021 Nov;9(11):755-766. doi: 10.1016/S2213-8587(21)00243-6. Epub 2021 Oct 4.
• McMurray JJV, Wheeler DC, Stefansson BV, Jongs N, Postmus D, Correa-Rotter R, Chertow GM, Hou FF, Rossing P, Sjostrom CD, Solomon SD, Toto RD, Langkilde AM, Heerspink HJL; DAPA-CKD Trial Committees and Investigators. Effects of Dapagliflozin in Patients With Kidney Disease, With and Without Heart Failure. JACC Heart Fail. 2021 Nov;9(11):807-820. doi: 10.1016/j.jchf.2021.06.017. Epub 2021 Aug 23.
• Persson F, Rossing P, Vart P, Chertow GM, Hou FF, Jongs N, McMurray JJV, Correa-Rotter R, Bajaj HS, Stefansson BV, Toto RD, Langkilde AM, Wheeler DC, Heerspink HJL; DAPA-CKD Trial Committees and Investigators. Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial. Diabetes Care. 2021 Aug;44(8):1894-1897. doi: 10.2337/dc21-0300. Epub 2021 Jun 28.
• Wheeler DC, Stefansson BV, Jongs N, Chertow GM, Greene T, Hou FF, McMurray JJV, Correa-Rotter R, Rossing P, Toto RD, Sjostrom CD, Langkilde AM, Heerspink HJL; DAPA-CKD Trial Committees and Investigators. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021 Jan;9(1):22-31. doi: 10.1016/S2213-8587(20)30369-7.
• McMurray JJV, Wheeler DC, Stefansson BV, Jongs N, Postmus D, Correa-Rotter R, Chertow GM, Greene T, Held C, Hou FF, Mann JFE, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Heerspink HJL; DAPA-CKD Trial Committees and Investigators. Effect of Dapagliflozin on Clinical Outcomes in Patients With Chronic Kidney Disease, With and Without Cardiovascular Disease. Circulation. 2021 Feb 2;143(5):438-448. doi: 10.1161/CIRCULATIONAHA.120.051675. Epub 2020 Nov 13.
• Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.
• Wheeler DC, Stefansson BV, Batiushin M, Bilchenko O, Cherney DZI, Chertow GM, Douthat W, Dwyer JP, Escudero E, Pecoits-Filho R, Furuland H, Gorriz JL, Greene T, Haller H, Hou FF, Kang SW, Isidto R, Khullar D, Mark PB, McMurray JJV, Kashihara N, Nowicki M, Persson F, Correa-Rotter R, Rossing P, Toto RD, Umanath K, Van Bui P, Wittmann I, Lindberg M, Sjostrom CD, Langkilde AM, Heerspink HJL. The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics. Nephrol Dial Transplant. 2020 Oct 1;35(10):1700-1711. doi: 10.1093/ndt/gfaa234.
• Piperidou A, Loutradis C, Sarafidis P. SGLT-2 inhibitors and nephroprotection: current evidence and future perspectives. J Hum Hypertens. 2021 Jan;35(1):12-25. doi: 10.1038/s41371-020-00393-4. Epub 2020 Aug 10.
• Sternlicht HK, Bakris GL. Reductions in albuminuria with SGLT2 inhibitors: a marker for improved renal outcomes in patients without diabetes? Lancet Diabetes Endocrinol. 2020 Jul;8(7):553-555. doi: 10.1016/S2213-8587(20)30185-6. No abstract available.
• Gonzalez DE, Foresto RD, Ribeiro AB. SGLT-2 inhibitors in diabetes: a focus on renoprotection. Rev Assoc Med Bras (1992). 2020 Jan 13;66Suppl 1(Suppl 1):s17-s24. doi: 10.1590/1806-9282.66.S1.17.

Drugs

Indications