Pharmacologic Heterogeneity and Risk of Severe Hypoglycemia with Concomitant Use of Sulfonylureas and <scp>DPP</scp>‐4 Inhibitors: Population‐Based Cohort Study
Bibliographic record
Abstract
Dipeptidyl peptidase-4 inhibitors (DPP-4i) interact with sulfonylureas to increase their risk of hypoglycemia. Our population-based study assessed whether intraclass pharmacologic heterogeneity among sulfonylureas (long- vs. short-acting) and DPP-4i (peptidomimetic vs. non-peptidomimetic) modifies this interaction. We conducted a cohort study using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data. We assembled a cohort of patients initiating sulfonylureas (2007-2020). Using a time-varying exposure definition, we assessed the risk of severe hypoglycemia (hospitalization with or death due to hypoglycemia) associated with (i) concomitant use of long-acting sulfonylureas (glimepiride and glibenclamide) with DPP-4i compared with concomitant use of short-acting sulfonylureas (gliclazide and glipizide) with DPP-4i; and (ii) concomitant use of sulfonylureas with peptidomimetic DPP-4i (saxagliptin and vildagliptin) compared with concomitant use of sulfonylureas with non-peptidomimetic DPP-4i (sitagliptin, linagliptin, and alogliptin). Time-dependent Cox models estimated confounder-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Our cohort included 196,138 sulfonylurea initiators. During a median follow-up of 6 years, 8,576 events of severe hypoglycemia occurred. Compared with concomitant use of short-acting sulfonylureas with DPP-4i, concomitant use of long-acting sulfonylureas with DPP-4i was not associated with the risk of severe hypoglycemia (adjusted HR: 0.87, 95% CI: 0.65-1.16). Compared with concomitant use of sulfonylureas with non-peptidomimetic DPP-4i, concomitant use of sulfonylureas with peptidomimetic DPP-4i was also not associated with the risk of severe hypoglycemia (HR: 0.96, 95% CI: 0.76-1.22). Intra-class pharmacologic heterogeneity did not modify the association between concomitant use of sulfonylureas (short- vs. long-acting) and DPP-4i (peptidomimetic vs. non-peptidomimetic) and the risk of severe hypoglycemia.
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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 | 0.005 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".