Rationale, design and baseline characteristics of REMODEL, a mechanism-of-action trial with semaglutide in people with type 2 diabetes and chronic kidney disease
Bibliographic record
Abstract
BACKGROUND: Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD) and kidney failure globally. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces the risk of major kidney, cardiovascular and mortality outcomes in people with T2D and CKD, but the mechanism of action remains unclear. METHODS: The REMODEL trial (NCT04865770) is a 52-week placebo-controlled, double-blind, parallel-group, randomized trial in adults with T2D and CKD. Inclusion criteria include haemoglobin A1c (HbA1c) ≤9%, estimated glomerular filtration rate (eGFR) ≥30-≤75 ml/min/1.73 m2 and urine albumin:creatinine ratio (UACR) ≥20-<5000 mg/g. The co-primary outcomes were magnetic resonance imaging (MRI) based, including change in kidney oxygenation, perfusion and inflammation. Secondary outcomes include change from baseline in creatine clearance rate, urinary sodium excretion, albumin excretion rate and kidney fibrosis and blood flow parameters measured by MRI. A subgroup had kidney biopsies at baseline and at the end of the treatment for tissue-based interrogation, including single nucleus and spatial transcriptomics, pathology and advanced histological assessment. RESULTS: Across eight countries, 106 participants (n = 33, biopsy subgroup) were enrolled. The mean age was 65.3 years [standard deviation (SD) 9.9] at baseline with HbA1c of 7.1% (SD 0.9), creatinine-based eGFR of 51.1 ml/min/1.73 m2 (SD 10.4) and median UACR of 187.3 mg/g (interquartile range 60.5-546.4). Renin-angiotensin system inhibitor use was 98.1% and sodium-glucose co-transporter 2 inhibitor use was 38.7%. In the kidney biopsy subgroup, baseline characteristics were like those of the full population. Histological analysis of kidney tissues revealed 17 participants with primarily diabetic nephropathy, 6 participants with primarily vascular features, 9 with mixed diabetic nephropathy and vascular characteristics and 1 with membranous nephropathy. CONCLUSION: The REMODEL trial leverages multipronged approaches to investigate the kidney-specific effects and underlying mechanisms of semaglutide in a representative population of people with T2D and CKD, which supports the generalizability and clinical relevance of the findings.
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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 | 0.022 | 0.015 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.016 | 0.005 |
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".