317-OR: Efficacy and Safety of Dapagliflozin by Glycemic Status in the DAPA-CKD Trial
Bibliographic record
Abstract
There is robust evidence that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of adverse cardiovascular and kidney outcomes. The DAPA-CKD trial (NCT03036150) demonstrated a significant risk reduction in participants with chronic kidney disease (CKD), with and without type 2 diabetes, treated with dapagliflozin 10 mg once daily compared with placebo, as an adjunct to standard care. In this prespecified analysis, we compared the efficacy and safety of dapagliflozin according to baseline glycemic status. The trial included individuals with CKD with an estimated glomerular filtration rate (eGFR) of 25 to 75 mL/min/1.73 m2 and a urinary albumin-to-creatinine ratio of 200 to 5000 mg/g. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes. We analyzed results by baseline glycemic status based on the American Diabetes Association criteria for HbA1c level <5.7% (normoglycemia) vs. ≥5.7 to <6.5% (prediabetes) vs. ≥6.5% or a history of type 2 diabetes. Of the 4304 participants in the trial, 738 had normoglycemia at baseline; 660, prediabetes; and 2906, type 2 diabetes. The relative risk reduction for the primary composite outcome with dapagliflozin (hazard ratio [HR], 0.61; 95% CI, 0.51−0.72) was consistent in participants with normoglycemia (HR, 0.62; 95% CI, 0.39−1.01), prediabetes (HR, 0.37; 95% CI, 0.21−0.66) and type 2 diabetes (HR, 0.64; 95% CI, 0.52−0.79; p-interaction = 0.19). Similarly, we found no evidence of effect modification by glycemic status on secondary or exploratory outcomes. The safety profile of dapagliflozin was similar across glycemic groups, with no events of major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes, and no ketoacidosis in any participant treated with dapagliflozin. In conclusion, dapagliflozin reduced the risk of kidney and cardiovascular events independent of baseline glycemic status. Disclosure F. Persson: Advisory Panel; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Mundipharma International, Novo Nordisk, Advisory Panel; Spouse/Partner; AstraZeneca, Bristol-Myers Squibb Company, Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Mundipharma International, Novo Nordisk. R. D. Toto: Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Medscape Education, Otsuka America Pharmaceutical, Inc., Quest Diagnostics, Reata Pharmaceuticals, Inc., Relypsa Inc. A. Langkilde: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. D. C. Wheeler: Advisory Panel; Self; Merck Sharp & Dohme Corp., Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, GlaxoSmithKline plc., Janssen Global Services, LLC., Mundipharma International, Tricida, Inc., Speaker’s Bureau; Self; Amgen Astellas BioPharma, Astellas Pharma Inc., Napp Pharmaceuticals, Vifor Pharma Management Ltd. H. L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook, CSL Behring, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, LLC, Merck & Co., Inc., Mitsubishi Corporation Life Sciences Limited, Mundipharma International, Novo Nordisk, Retrophin, Inc., Research Support; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC. Dapa-ckd study group: n/a. P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. P. Vart: None. G. M. Chertow: Advisory Panel; Self; Ardelyx, Baxter, Cricket Health, DURECT Corporation, Gilead Sciences, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Self; Akebia Therapeutics, Inc., AstraZeneca, Vertex Pharmaceuticals Incorporated. F. Hou: Consultant; Self; AstraZeneca. J. J. Mcmurray: Other Relationship; Self; AbbVie Inc., Amgen Inc., AstraZeneca, Bayer AG, Cytokinetics Inc., DalCor Pharmaceuticals, Merck & Co., Inc., Novartis AG, Servier Laboratories, Theracos, Inc. R. Correa-rotter: Consultant; Self; GlaxoSmithKline plc., Other Relationship; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Novo Nordisk Inc., Speaker’s Bureau; Self; AbbVie Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceutical Co. H. S. Bajaj: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., Sanofi, Tricida, Inc. B. Stefansson: Employee; Self; AstraZeneca. Funding AstraZeneca
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".