The modifying effects of adiposity on the cardiovascular safety of sulphonylureas
Bibliographic record
Abstract
Abstract Aims To determine whether adiposity modified the effect on the cardiovascular safety of sulphonylureas as a first‐line therapy compared with metformin among patients with type 2 diabetes. Materials and Methods Using the UK Clinical Practice Research Datalink, we conducted a cohort study among 13 862 new sulphonylurea users matched on body mass index (BMI) and propensity score, in a 1:1 ratio, to new metformin users between April 1, 1998 and December 31, 2016. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of major adverse cardiovascular events (MACE), individual components of MACE (myocardial infarction [MI], ischaemic stroke, cardiovascular mortality), and all‐cause mortality, comparing use of sulphonylureas with use of metformin, overall and within BMI categories (≤24.9 kg/m 2 , 25.0‐29.9 kg/m 2 , ≥30 kg/m 2 ). Results Compared with metformin, sulphonylureas were not associated with an increased risk of MACE either overall (HR 1.08, 95% CI 0.94‐1.23) or by BMI category. Similar findings were observed for MI and ischaemic stroke. By contrast, sulphonylureas were associated with an increased risk of cardiovascular mortality (HR 1.24, 95% CI 1.04‐1.48), primarily among obese patients (HR 1.52, 95% CI 1.08‐2.13), and not among normal‐weight patients (HR 1.00, 95% CI 0.72‐1.39; P‐interaction 0.21). Similar results were observed for all‐cause mortality (HR 1.47, 95% CI 1.32‐1.62), where an increased risk was observed among obese patients (HR 1.83, 95% CI 1.49‐2.25), but not normal‐weight patients (HR 1.18, 95% CI 0.99‐1.42; P‐interaction : 0.006). Conclusion The findings of this study suggest that adiposity may have a modifying effect on the association between sulphonylureas and cardiovascular and all‐cause mortality compared with metformin.
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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 | 0.002 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".