130-LB: Dapagliflozin and the Incidence of Type 2 Diabetes in Patients with Chronic Kidney Disease
Bibliographic record
Abstract
The DAPA-CKD trial demonstrated a significant reduction in the risk of adverse kidney and cardiovascular outcomes in participants with chronic kidney disease (CKD), with and without type 2 diabetes (T2D), treated with dapagliflozin 10 mg once daily compared to placebo (randomized 1:1). This pre-specified analysis explored the effect of dapagliflozin on incident T2D in the cohort without diabetes enrolled in DAPA-CKD. A subgroup of 1,398 participants with CKD, no prior history of diabetes, and HbA1c <6.5% at baseline were included. In this pre-specified exploratory analysis, surveillance for new-onset T2D (confirmed HbA1c ≥6.5%) was accomplished through periodic HbA1c testing (part of the study protocol) and comparison between treatment groups assessed through Cox proportional hazards model. Over a median follow-up of 2.4 years, T2D developed in 33/701 (4.7%) in the placebo group and 21/697 (3.0%) in the dapagliflozin group. This corresponded to event rates of 2.4/100-patient years and 1.5/100-patient years, respectively. Dapagliflozin led to a 38% reduction in T2D incidence (hazard ratio [95%CI] 0.62 [0.36, 1.08]). There was no heterogeneity in the effect of dapagliflozin on T2D prevention based on most key prespecified subgroups, including age, glycemic status, blood pressure, estimated glomerular filtration rate, albuminuria, race and region, but the effect was more pronounced in females (p interaction 0.03). More than 90% of the participants who developed T2D had prediabetes at baseline (HbA1c 5.7-6.4%). A meta-analysis of DAPA-CKD and DAPA-HF (dapagliflozin in heart failure with reduced ejection fraction) demonstrated that dapagliflozin reduced new-onset diabetes compared to placebo (hazard ratio 0.66 [0.51, 0.87]; p=0.003), without heterogeneity between studies (p interaction 0.78). In this pre-specified explorative analysis of patients with CKD, treatment with dapagliflozin reduced the incidence of new T2D, an effect that was consistent across DAPA-CKD and DAPA-HF. Disclosure 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. 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. 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. N. Jongs: None. 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. B. Stefansson: Employee; Self; AstraZeneca. 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. 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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".