Association of Dipeptidyl Peptidase-4 Inhibitors with Glaucoma Risk in Patients with Type 2 Diabetes: A Nationwide Cohort Study
Purpose: To investigate the association between dipeptidyl peptidase-4 inhibitors (DPP4is) and the risk of primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in patients with type 2 diabetes mellitus (T2DM). Design: Retrospective cohort study. Subjects: A total of 582 710 patients...
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Elsevier
2025-09-01
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| Series: | Ophthalmology Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666914525001253 |
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| author | Yi-An Lu, MD Peng-Tai Tien, MD, PhD Yih-Dih Cheng, PhD Yow-Wen Hsieh, PhD Der-Yang Cho, MD Shang-Feng Tsai, MD, PhD Chien-Hsiang Weng, MD, MPH Heng-Jun Lin Hui-Ju Lin, MD, PhD I-Jong Wang, MD, PhD Chien-Chih Chou, MD, PhD |
| author_facet | Yi-An Lu, MD Peng-Tai Tien, MD, PhD Yih-Dih Cheng, PhD Yow-Wen Hsieh, PhD Der-Yang Cho, MD Shang-Feng Tsai, MD, PhD Chien-Hsiang Weng, MD, MPH Heng-Jun Lin Hui-Ju Lin, MD, PhD I-Jong Wang, MD, PhD Chien-Chih Chou, MD, PhD |
| author_sort | Yi-An Lu, MD |
| collection | DOAJ |
| description | Purpose: To investigate the association between dipeptidyl peptidase-4 inhibitors (DPP4is) and the risk of primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in patients with type 2 diabetes mellitus (T2DM). Design: Retrospective cohort study. Subjects: A total of 582 710 patients with T2DM treated with either DPP4i (exposure group) or non-DPP4i medications (control group) were analyzed between 2008 and 2021. Methods: Patients were 1-to-1 matched by propensity scores on demographic and clinical characteristics. Cox proportional hazards models were applied to estimate hazard ratios for POAG and NTG, adjusting for age, sex, comorbidities, and concurrent antidiabetic medications. Main Outcome Measures: Incidences of POAG and NTG. Results: Dipeptidyl peptidase-4 inhibitor users demonstrated a significantly lower risk of POAG (adjusted hazard ratio [aHR], 0.53; 95% confidence interval [CI], 0.50–0.56) and NTG (aHR, 0.55; 95% CI, 0.50–0.62) compared to non-DPP4i users on first-generation diabetes medication. Subgroup analysis revealed a consistent risk reduction across all age groups (18–39: aHR, 0.56; 95% CI, 0.51–0.62; 40–64: aHR, 0.52; 95% CI, 0.47–0.57; ≥65 years: aHR, 0.51; 95% CI, 0.47–0.56) and among patients with or without diabetic-related complications, including diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy (DN) (aHR: without vs. with diabetic retinopathy [0.54 vs. 0.43], without vs. with diabetic kidney disease [0.53 vs. 0.49], without vs. with DN [0.54 vs.0.43]), with all comparisons showing statistical significance (P < 0.001). Cumulative incidence analyses revealed a sustained lower risk for DPP4i users throughout the study period (log-rank P < 0.001). Conclusions: Exposure to DPP4i was associated with a reduced risk of developing POAG and NTG compared with users of first-generation diabetes medication. Further research is needed to explore the underlying mechanisms and their implications for glaucoma prevention and management. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. |
| format | Article |
| id | doaj-art-8b62dee4d3214e208771e77435a98d75 |
| institution | OA Journals |
| issn | 2666-9145 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ophthalmology Science |
| spelling | doaj-art-8b62dee4d3214e208771e77435a98d752025-08-20T02:10:03ZengElsevierOphthalmology Science2666-91452025-09-015510082710.1016/j.xops.2025.100827Association of Dipeptidyl Peptidase-4 Inhibitors with Glaucoma Risk in Patients with Type 2 Diabetes: A Nationwide Cohort StudyYi-An Lu, MD0Peng-Tai Tien, MD, PhD1Yih-Dih Cheng, PhD2Yow-Wen Hsieh, PhD3Der-Yang Cho, MD4Shang-Feng Tsai, MD, PhD5Chien-Hsiang Weng, MD, MPH6Heng-Jun Lin7Hui-Ju Lin, MD, PhD8I-Jong Wang, MD, PhD9Chien-Chih Chou, MD, PhD10Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, TaiwanEye Center, China Medical University Hospital, Taichung, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung, TaiwanDepartment of Pharmacy, China Medical University Hospital, Taichung, Taiwan; School of Pharmacy, China Medical University, Taichung, TaiwanDepartment of Pharmacy, China Medical University Hospital, Taichung, Taiwan; School of Pharmacy, China Medical University, Taichung, TaiwanTranslational Cell Therapy Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, TaiwanDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Life Science, Tunghai University, Taichung, TaiwanDepartment of Family Medicine, Brown University Warren Alpert Medical School, Providence, Rhode Island; Brown Health Medical Group Primary Care, Brown University Health, Providence, Rhode IslandManagement Office for Health Data, China Medical University Hospital, Taichung, TaiwanEye Center, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Department of Ophthalmology, National Taiwan University Hospital, Taipei, TaiwanDepartment of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Correspondence: Chien-Chih Chou, MD, PhD, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St., Beitou Dist., Taipei, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Xitun Dist., Taichung, Taiwan.Purpose: To investigate the association between dipeptidyl peptidase-4 inhibitors (DPP4is) and the risk of primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in patients with type 2 diabetes mellitus (T2DM). Design: Retrospective cohort study. Subjects: A total of 582 710 patients with T2DM treated with either DPP4i (exposure group) or non-DPP4i medications (control group) were analyzed between 2008 and 2021. Methods: Patients were 1-to-1 matched by propensity scores on demographic and clinical characteristics. Cox proportional hazards models were applied to estimate hazard ratios for POAG and NTG, adjusting for age, sex, comorbidities, and concurrent antidiabetic medications. Main Outcome Measures: Incidences of POAG and NTG. Results: Dipeptidyl peptidase-4 inhibitor users demonstrated a significantly lower risk of POAG (adjusted hazard ratio [aHR], 0.53; 95% confidence interval [CI], 0.50–0.56) and NTG (aHR, 0.55; 95% CI, 0.50–0.62) compared to non-DPP4i users on first-generation diabetes medication. Subgroup analysis revealed a consistent risk reduction across all age groups (18–39: aHR, 0.56; 95% CI, 0.51–0.62; 40–64: aHR, 0.52; 95% CI, 0.47–0.57; ≥65 years: aHR, 0.51; 95% CI, 0.47–0.56) and among patients with or without diabetic-related complications, including diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy (DN) (aHR: without vs. with diabetic retinopathy [0.54 vs. 0.43], without vs. with diabetic kidney disease [0.53 vs. 0.49], without vs. with DN [0.54 vs.0.43]), with all comparisons showing statistical significance (P < 0.001). Cumulative incidence analyses revealed a sustained lower risk for DPP4i users throughout the study period (log-rank P < 0.001). Conclusions: Exposure to DPP4i was associated with a reduced risk of developing POAG and NTG compared with users of first-generation diabetes medication. Further research is needed to explore the underlying mechanisms and their implications for glaucoma prevention and management. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.http://www.sciencedirect.com/science/article/pii/S2666914525001253Dipeptidyl peptidase-4 inhibitorsNormal tension glaucomaOcular hypertensionPrimary open-angle glaucomaType 2 diabetes mellitus |
| spellingShingle | Yi-An Lu, MD Peng-Tai Tien, MD, PhD Yih-Dih Cheng, PhD Yow-Wen Hsieh, PhD Der-Yang Cho, MD Shang-Feng Tsai, MD, PhD Chien-Hsiang Weng, MD, MPH Heng-Jun Lin Hui-Ju Lin, MD, PhD I-Jong Wang, MD, PhD Chien-Chih Chou, MD, PhD Association of Dipeptidyl Peptidase-4 Inhibitors with Glaucoma Risk in Patients with Type 2 Diabetes: A Nationwide Cohort Study Ophthalmology Science Dipeptidyl peptidase-4 inhibitors Normal tension glaucoma Ocular hypertension Primary open-angle glaucoma Type 2 diabetes mellitus |
| title | Association of Dipeptidyl Peptidase-4 Inhibitors with Glaucoma Risk in Patients with Type 2 Diabetes: A Nationwide Cohort Study |
| title_full | Association of Dipeptidyl Peptidase-4 Inhibitors with Glaucoma Risk in Patients with Type 2 Diabetes: A Nationwide Cohort Study |
| title_fullStr | Association of Dipeptidyl Peptidase-4 Inhibitors with Glaucoma Risk in Patients with Type 2 Diabetes: A Nationwide Cohort Study |
| title_full_unstemmed | Association of Dipeptidyl Peptidase-4 Inhibitors with Glaucoma Risk in Patients with Type 2 Diabetes: A Nationwide Cohort Study |
| title_short | Association of Dipeptidyl Peptidase-4 Inhibitors with Glaucoma Risk in Patients with Type 2 Diabetes: A Nationwide Cohort Study |
| title_sort | association of dipeptidyl peptidase 4 inhibitors with glaucoma risk in patients with type 2 diabetes a nationwide cohort study |
| topic | Dipeptidyl peptidase-4 inhibitors Normal tension glaucoma Ocular hypertension Primary open-angle glaucoma Type 2 diabetes mellitus |
| url | http://www.sciencedirect.com/science/article/pii/S2666914525001253 |
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