Sodium‐glucose cotransporter‐2 inhibitor initiation and incident dementia in heart failure with diabetes: a population‐based cohort study
Bibliographic record
Abstract
BACKGROUND: People with heart failure have an increased risk of developing dementia. Commonly comorbid diseases such as diabetes, atrial fibrillation, and hypertension can further elevate dementia risk. However, people with heart failure are underrepresented in clinical trials for dementia. This study aims to determine whether sodium-glucose cotransporter-2 inhibitors (SGLT2i) use is associated with a lower risk of dementia in people with heart failure and comorbid diabetes. METHOD: , 2020, entered this cohort. DPP4i was selected as an active comparator to reduce confounding by indication. A 180-day lag time was implemented to mitigate reverse causation. The primary analysis used an intention-to-treat exposure definition. Propensity score fine stratification weights were used to adjust for baseline covariates, including demographics, comorbidities, procedures, medications, healthcare utilization, and disease-related variables. The definition of dementia was adapted from previously validated algorithms. Cause-specific hazard ratios (HRs) with death as a competing risk were estimated, using weighted Cox regression models. RESULT: Among 4,402 SGLT2i and 6,319 DPP4i new users, the mean age was 76.4 years, and 39.7% were female. Over a median follow-up of 3.95 years from cohort entry, SGLT2i versus DPP4i initiation was associated with a 26% lower risk of incident dementia (HR 0.74, 95% confidence interval 0.61-0.89; incidence rate: 21.8 versus 29.5 events per 1,000 person-years). Associations between SGLT2i initiation and a lower dementia risk persisted in subgroups with atrial fibrillation (0.66, 0.51-0.85; 20.6 versus 31.2) or those aged ≥75 years (0.62, 0.50-0.78; 26.9 versus 43.1). The secondary as-treated analysis showed greater dementia risk reduction (0.54, 0.40-0.73; 16.3 versus 30.1). CONCLUSION: SGLT2i initiation was associated with a lower risk of dementia in people with heart failure and diabetes, particularly in high-risk subgroups for dementia. The findings suggest that SGLT2i may prevent dementia in these high-risk populations, representing new opportunities for randomized controlled trials.
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 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) | 0.002 | 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".