Cardiovascular outcomes in patients with type 2 diabetes and reduced eGFR and albuminuria: a REWIND post hoc subgroup analysis
Bibliographic record
Abstract
Abstract Background/Introduction Diabetic kidney disease affects up to 40% of people with diabetes and is associated with higher cardiovascular (CV) risk. REWIND was a multicentre, randomised, double-blind, placebo-controlled trial with a primary outcome of first occurrence of the composite endpoint of CV death, nonfatal myocardial infarction, or nonfatal stroke (Major Adverse Cardiovascular Event [MACE]-3). Dulaglutide treatment reduced the incidence of MACE-3 in patients with type 2 diabetes (T2D) with or without established CV disease. Purpose This REWIND post hoc subgroup analysis evaluated the effect of dulaglutide on MACE-3 in patients with an eGFR<60 and ≥60 mL/min/1.73m2 and patients with micro-/macro-albuminuria (UACR ≥30 mg/g) or normoalbuminuria (UACR <30 mg/g). Methods Eligible patients were those ≥50 years old with T2D who had either a previous CV event or CV risk factors. Patients were randomised (1:1) to dulaglutide 1.5 mg or placebo, both in addition to standard of care. A Cox proportional hazards model with treatment, eGFR subgroup (<60 and ≥60 mL/min/1.73 m2), and treatment by eGFR subgroup interaction was used to analyse time to the first occurrence of MACE-3. These analyses were also conducted for albuminuria subgroups (micro-/macro-albuminuria or normoalbuminuria). Estimates of hazard ratios (HR) with 95% confidence intervals (CI) were calculated for each subgroup. Results At baseline, 2,199 of 9,901 patients (22.2%) had an eGFR <60 mL/min/1.73 m2, 2,676 (27.0%) had microalbuminuria, and 791 (8.0%) had macroalbuminuria. This post hoc subgroup analysis showed that dulaglutide treatment was consistently associated with MACE-3 risk reduction in patients with eGFR <60 and ≥60 mL/min/1.73 m2 (HR [95% CI]: 0.93 [0.76–1.13] and 0.86 [0.75–0.99], respectively; interaction p=0.545). Similarly, MACE-3 risk reduction was consistent in patients with micro-/macro-albuminuria or normoalbuminuria (HR [95% CI]: 0.84 [0.72–0.99] and 0.93 [0.79–1.10], respectively; interaction p=0.374). Conclusions Regardless of baseline eGFR or albuminuria status, dulaglutide reduces MACE-3 outcomes in patients with T2D and established CV disease or multiple CV risk factors. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Eli Lilly and Company
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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 | 0.009 | 0.009 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.008 | 0.017 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.000 |
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".