Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs Glucagonlike Peptide-1 Receptor Agonists and Incidence of Dry Eye Disease in Patients with Type 2 Diabetes in Taiwan

Importance: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to improve low-grade systemic and tissue inflammation; however, the association between SGLT2 inhibitor use and the incidence of dry eye disease (DED) has not been explored. Objective: To investigate the association between SGLT2 inhibitor use and dry eye disease in patients with type 2 diabetes (T2D). Design, Setting, and Participants: A retrospective cohort analysis of the largest multi-institutional electronic medical records database in Taiwan was conducted to identify patients with T2D newly receiving SGLT2 inhibitors or glucagonlike peptide-1 receptor agonists (GLP-1 RAs) from 2016 to 2018. Data analysis was performed from March 1 to May 31, 2022. Propensity scores with inverse probability of treatment weighting were generated to enable homogeneous comparisons between the 2 groups. Exposures: Treatment with SGLT2 inhibitors or GLP-1 RAs. Main Outcomes and Measures: Incident dry eye disease, which was defined by clinical diagnoses, plus the related drug prescription. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for the risk of DED. Results: A total of 10038 and 1077 T2D patients newly receiving SGLT2 inhibitors (mean [SD] age, 59.5 [12.1] years; 5689 [56.7%] men) or GLP-1 RAs (mean [SD] age, 58.5 [41.2] years; 587 [54.5%] men), respectively, were included in the analysis. The incidence of DED was lower in patients newly receiving SGLT2 inhibitors (9.0 events per 1000 person-years) compared with those receiving GLP-1 RAs (11.5 events per 1000 person-years), yielding a hazard ratio of 0.78 (95% CI, 0.68-0.89). Subgroup analyses indicated that the lowered DED risks associated with SGLT2 inhibitors in patients with T2D were similar across different age, sex, blood glucose level, and kidney function groups. Results from the sensitivity analyses (including the propensity score-matching approach, on-treatment analyses, and different follow-up periods of 1, 2, and 3 years) were similar to the main analyses. Conclusions and Relevance: The findings of this study suggest that patients with T2D newly receiving SGLT2 inhibitors may have a lower risk for DED compared with those receiving GLP-1 RAs. Prospective studies are needed to analyze these results..