Effects of Semaglutide on CKD Outcomes: A Post Hoc Pooled Analysis from the SUSTAIN 6 and PIONEER 6 Trials
Bibliographic record
Abstract
Background: The SUSTAIN 6 cardiovascular outcomes trial (CVOT) indicated a benefit on kidney disease with subcutaneous (s.c.) once-weekly (OW) semaglutide vs placebo (PBO) in subjects with type 2 diabetes (T2D) at high CV risk. The PIONEER 6 CVOT reported CV safety with oral once-daily (OD) semaglutide in a similar cohort. This post hoc analysis evaluated the potential benefit of semaglutide vs PBO on chronic kidney disease (CKD) outcomes. Methods: Data from 6,480 subjects (SUSTAIN 6: N=3,297; median follow-up, 2.1 years; mean baseline [BL] estimated glomerular filtration rate [eGFR], 76 mL/min/1.73 m2; PIONEER 6: N=3,183; median follow-up, 1.3 years; mean BL eGFR, 74 mL/min/1.73 m2) were pooled for semaglutide (0.5 and 1.0 mg s.c. OW, 14 mg oral OD) or PBO. Time to onset of persistent eGFR reduction (≥30, ≥40, ≥50, ≥57% [corresponding to doubling of serum creatinine]) was evaluated overall and by BL eGFR subgroup (≥30-<60, ≥60 mL/min/1.73 m2). Analyses used a Cox proportional-hazards model with treatment group and eGFR subgroup and interaction between both as fixed factors stratified by trial. Results: In the overall population, hazard ratios (HRs) for onset of persistent eGFR reductions with semaglutide vs PBO were not statistically significantly different from 1, but estimated HRs were <1.0, favoring semaglutide. Estimated HRs for semaglutide vs PBO in the eGFR ≥30-<60 mL/min/1.73 m2 subgroup were generally lower than in the overall population; semaglutide significantly reduced the risk of developing a persistent 30% eGFR reduction vs PBO (p=0.03; Figure). No significant interactions between treatment and eGFR subgroup were observed. Conclusions: This analysis of semaglutide CVOTs supports the possibility of a smaller magnitude of eGFR decline with semaglutide vs PBO and suggests a potential kidney disease benefit of semaglutide vs PBO in people with T2D and established CKD. Funding: Commercial Support - Novo Nordisk
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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 | 0.013 | 0.011 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.016 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".