Background: The sodium-glucose cotransporter 2 inhibitor dapagliflozin improved kidney and cardiovascular (CV) outcomes in persons with chronic kidney disease (CKD) with and without type 2 diabetes (T2D) in the DAPA-CKD study. In this prespecified analysis we investigate the effects of dapagliflozin on kidney, CV, and mortality outcomes according to baseline diabetes drug class or number of diabetes drugs.

Methods: We enrolled participants with CKD with eGFR 25-75 ml/min/1.73m2 and UACR 200-5000 mg/g, and included those with T2D at baseline in this analysis. The primary endpoint was a composite of sustained decline in eGFR of ≥50%, end-stage kidney disease, or death from kidney or CV causes. Secondary outcomes included a kidney-specific composite (the same as the primary without CV death) , composite of hospitalizations for heart failure and CV mortality, and all-cause mortality. We determined the effect of dapagliflozin, compared with placebo, in subgroups by use or not of diabetes drug classes at baseline: metformin, sulfonylureas, DPP4 inhibitors, GLP-1 receptor agonists and insulin, and by the number of diabetes medications at baseline.

Results: Of 43participants enrolled 29 (68%) had T2D, of which 1598 (55%) were on insulin, 1244 (43%) on metformin, 774 (27%) on sulfonylureas, 742 (26%) on DPP4 inhibitors, and 122 (4%) on GLP-1 receptor agonists. At baseline 327 (11%) were without diabetes treatment, 1442 (50%) were treated with one diabetes drug, 943 (32%) with two drugs and 194 (7%) with three or more. The effect of dapagliflozin on the primary composite outcome was consistent across comparisons of baseline drug class (all pint>0.19) , and according to number of drugs (pint=0.08) . Similarly, we found consistent benefit of dapagliflozin compared to placebo on the secondary endpoints regardless of background drug class or number of drugs.

Conclusion: Dapagliflozin reduced kidney and CV events in T2D with CKD independent of baseline diabetes drug class or number.

Disclosure

F.Persson: Advisory Panel; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Research Support; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi. R.D.Toto: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Chinook Therapeutics Inc., Lilly, Consultant; Amgen Inc., AstraZeneca, Medscape, Vifor Pharma Management Ltd., Other Relationship; Akebia Therapeutics, Inc., Otsuka America Pharmaceutical, Inc., Reata Pharmaceuticals, Inc. A.Langkilde: Employee; AstraZeneca, Stock/Shareholder; AstraZeneca. D.C.Wheeler: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., GlaxoSmithKline plc., Janssen Global Services, LLC, Merck Sharp & Dohme Corp., Mundipharma, Tricida, Inc., Vifor Pharma Management Ltd., Consultant; AstraZeneca, Speaker's Bureau; Amgen Inc., Astellas Pharma Inc. H.L.Heerspink: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., Goldfinch Bio, Inc., Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Mundipharma, Traveere Pharmaceuticals, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Dapa-ckd trial committees and investigators: n/a. P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. N.Jongs: None. G.M.Chertow: Other Relationship; AstraZeneca. F.Hou: Other Relationship; AstraZeneca. P.Vart: None. J.J.Mcmurray: Other Relationship; Abbott, Alkem Metabolics, Alnylam Pharmaceuticals, Inc., Amgen Inc., AstraZeneca, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Cardurion, Cytokinetics Inc., DalCor Pharmaceuticals, Eris Lifesciences Ltd., GlaxoSmithKline plc., Ionis Pharmaceuticals, KBP Bioscience, Lupin Pharmaceuticals, Inc., Medscape, Novartis AG, ProAdWise Communications, Radcliffe Group, Servier Laboratories, Sun Pharmaceutical Industries Ltd., The Corpus, Theracos, Inc. R.Correa-rotter: Advisory Panel; Boehringer Ingelheim International GmbH, Consultant; Bayer AG, Other Relationship; AstraZeneca, GlaxoSmithKline plc., Novo Nordisk, Speaker's Bureau; AbbVie Inc., Amgen Inc., Janssen Pharmaceuticals, Inc., Sanofi. B.Stefansson: Employee; AstraZeneca.

Funding

AstraZeneca

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