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Comparative risk of the neurodegenerative outcomes between sodium-glucose co-transporter 2 (SGLT2) inhibitors and thiazolidinediones in type 2 diabetes: a multicentre cohort study using the Korean healthcare database (2014-2025)

Por: Park · S. J. · Kim · H. J. · Seo · M. · Byun · D. W. · Suh · K. · Yoo · M. H. · Yang · H. · Lee · I. · Kwon · S. H. · Kim · M. · Mok · J.-O. · Kim · D.-Y. · Sohn · S. Y. · Park · R. W. · Seo · W.-W. · Kwon · S. Y. · Rhee · S. Y. · Kwon · J.-M. · Cha · J. M. · Park · H. K.
Objective

Type 2 diabetes mellitus has been associated with an increased risk of cognitive decline and dementia, with patients being 1.5–2 times more likely to develop these conditions. While both sodium-glucose co-transporter 2 (SGLT2) inhibitors and thiazolidinediones (TZDs) have shown potential neuroprotective effects in previous studies, their comparative effectiveness for preventing neurodegenerative outcomes has not been established. This study aimed to compare the risk of stroke, dementia and Alzheimer’s disease (AD) between patients treated with SGLT2 inhibitors and those treated with TZDs.

Design

Multicentre, retrospective, observational, new-user, active-comparator cohort study.

Setting

Electronic health record-based databases from 11 secondary and tertiary institutions in South Korea from 1 January 2014 to 31 July 2025. The study period began in 2014, following the post-marketing surveillance initiation of SGLT2 inhibitors in Korea (November 2013), to ensure adequate drug availability and clinical adoption.

Participants

Patients aged 40 years or older who were newly prescribed either SGLT2 inhibitors or TZDs without prior exposure.

Interventions

Propensity score matching (1:1) was performed using sex as the primary covariate due to data availability constraints in the Observational Medical Outcomes Partnership Common Data Model framework. The HRs with 95% CIs were measured via Cox regression analysis.

Results

The study analysed 24 172 matched pairs for stroke outcomes (40 483 person-years in the SGLT2 inhibitor group and 39 363 person-years in the TZD group), 25 111 matched pairs for dementia (41 924 person-years in the SGLT2 inhibitor group and 40 726 person-years in the TZD group) and 25 237 matched pairs for AD (42 139 person-years in the SGLT2 inhibitor group and 40 895 person-years in the TZD group) across 11 participating hospitals. After a 1:1 propensity score matching, the SGLT2 inhibitors showed no significant difference in stroke risk (HR 1.18, 95% CI 0.62 to 2.23, p=0.62), while having significant reductions in dementia risk (HR 0.66, 95% CI 0.45 to 0.98, p=0.04) and AD risk (HR 0.54, 95% CI 0.35 to 0.83, p=0.005). Moreover, these protective effects for neurodegenerative outcomes were shown to be consistent across multiple hospital sites.

Conclusions

SGLT2 inhibitors are associated with a reduced risk of dementia and AD compared with TZDs in patients aged 40 years or older with type 2 diabetes and have neutral effects on stroke risk. These findings confirm the potential selective neuroprotective benefits of SGLT2 inhibitors for neurodegenerative outcomes, which may inform therapeutic decision-making for diabetic patients at risk of cognitive decline.

Association between pneumoconiosis and cataract risk: a nationwide retrospective cohort study in Taiwan

Por: Cheng · J.-S. · Lin · Y.-S. · Lin · C.-L. · Hsia · N.-Y. · Shen · T.-C. · Cho · D.-Y.
Objectives

To investigate whether pneumoconiosis increases the risk of cataract.

Design

Nationwide population-based retrospective cohort study.

Setting

Taiwan’s National Health Insurance database, which covers >99% of the population.

Participants

The study included 19 841 adults newly diagnosed with pneumoconiosis between 2001 and 2020 and 79 364 age-matched and sex-matched individuals without pneumoconiosis. Participants with a prior history of cataract were excluded.

Outcome measures

The primary outcome was incident cataract identified through International Classification of Diseases diagnostic codes. Subgroup analyses were performed to evaluate cataract risk across different strata of age, sex and comorbidity. In addition, among patients with pneumoconiosis, we conducted a secondary analysis evaluating the association between systemic corticosteroid use and cataract development.

Results

During follow-up, the incidence of cataract was significantly higher in the pneumoconiosis cohort (38.9 vs 35.3 per 1000 person-years). Patients with pneumoconiosis had an increased risk of cataract after adjustment for age, sex and comorbidities (adjusted HR (aHR)=1.22, 95% CI 1.18 to 1.26). Elevated risks were observed in both men (aHR=1.22, 95% CI 1.18 to 1.26) and women (aHR=1.20, 95% CI 1.13 to 1.29). All age groups showed increased risks, with the highest estimate observed among patients aged ≥75 years (aHR=1.24, 95% CI 1.19 to 1.30). Subgroup analyses showed an increased risk in patients with pneumoconiosis who had no comorbidities (aHR=1.12, 95% CI 1.07 to 1.18). In a secondary analysis, systemic corticosteroid exposure was not significantly associated with cataract development (adjusted OR=0.65, 95% CI 0.39 to 1.09).

Conclusions

Pneumoconiosis is associated with an increased risk of cataract. Routine ophthalmologic surveillance should be considered in pneumoconiosis management.

Risk of cataract in patients with systemic lupus erythematosus: a retrospective cohort study in Taiwan

Por: Liu · D.-Y. · Chung · C. · Wang · Y.-T. · Lee · H.-M. · Cheng · T.-A. · Lin · C.-A. · Su · Y.-C. · Yao · P.-T. · Shen · T.-C. · Lin · H.-J. · Tsai · F.-J.
Objectives

To investigate whether systemic lupus erythematosus (SLE) increases the risk of cataract development and to evaluate the impact of corticosteroid use and dosage on this risk.

Design

Nationwide retrospective cohort study.

Setting

Using Taiwan’s National Health Insurance (NHI) database, which covers over 99.9% of the population.

Participants

The SLE cohort included 30 501 newly diagnosed adults from 2011 to 2020. For each patient with SLE, four individuals without SLE were selected from the NHI database using frequency matching by age (in 5 year intervals), gender and index year of diagnosis, resulting in a comparison cohort of 122 004 individuals.

Primary and secondary outcome measures

The primary outcome was incident cataract. Secondary outcomes included risk stratification by age, sex, comorbidities and corticosteroid dose.

Results

SLE patients had a higher incidence of cataracts than non-SLE individuals (adjusted HR (aHR) = 1.73, 95% CI 1.66 to 1.81). Stratified analyses showed elevated risks in women (aHR=1.74, 95% CI 1.66 to 1.83), men (aHR=1.68, 95% CI 1.52 to 1.86), and across age groups 20–49 years (aHR=2.32, 95% CI 2.11 to 2.56), 50–64 years (aHR=1.60, 95% CI 1.51 to 1.69), and ≥65 years (aHR=1.50, 95% CI 1.36 to 1.66). Analysis of corticosteroid exposure revealed that cumulative dose showed a trend towards increased risk at high exposure (adjusted OR (aOR) = 1.14, 95% CI 0.99 to 1.31), while average daily dose demonstrated a dose–response effect: 1–5 mg/day (aOR=1.31, 95% CI 1.13 to 1.52) and ≥5 mg/day (OR=2.48, 95% CI 2.16 to 2.86).

Conclusions

Adults with SLE have an increased risk of developing cataracts compared with matched controls, and higher average daily corticosteroid doses are associated with this risk. These findings highlight the need for careful monitoring of ocular complications in SLE patients.

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