Association of Dipeptidyl Peptidase-4 Inhibitors with Glaucoma Risk in Patients with Type 2 Diabetes: A Nationwide Cohort Study

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-05-14 DOI:10.1016/j.xops.2025.100827

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

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Abstract

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.

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二肽基肽酶-4抑制剂与2型糖尿病患者青光眼风险的关系：一项全国性队列研究

目的探讨二肽基肽酶-4抑制剂（DPP4is）与2型糖尿病（T2DM）患者原发性开角型青光眼（POAG）和正常张力型青光眼（NTG）发病的关系。设计回顾性队列研究。研究对象：2008年至2021年间，共有582710例T2DM患者接受DPP4i（暴露组）或非DPP4i药物（对照组）治疗。方法采用人口统计学和临床特征倾向性评分进行1对1匹配。Cox比例风险模型用于估计POAG和NTG的风险比，调整年龄、性别、合并症和并发抗糖尿病药物。主要观察指标：POAG和NTG的发生率。结果二肽基肽酶-4抑制剂使用者发生POAG的风险显著降低(校正风险比[aHR]， 0.53；95%可信区间[CI]， 0.50-0.56)和NTG (aHR, 0.55；95% CI, 0.50-0.62)，与第一代糖尿病药物非dpp4i使用者相比。亚组分析显示，所有年龄组的风险降低一致(18-39岁：aHR， 0.56；95% ci, 0.51-0.62；40-64: aHR 0.52；95% ci, 0.47-0.57；≥65岁：aHR， 0.51；95% CI, 0.47-0.56)，以及有无糖尿病相关并发症（包括糖尿病视网膜病变、糖尿病肾病和糖尿病神经病变（DN））的患者（aHR：有无糖尿病视网膜病变vs.0.43，有无糖尿病肾病vs. 0.53，有无DN [0.54 vs.0.43]），比较均有统计学意义(P <；0.001)。累积发生率分析显示，在整个研究期间，DPP4i使用者的风险持续降低(log-rank P <；0.001)。结论与第一代糖尿病药物使用者相比，暴露于DPP4i与发生POAG和NTG的风险降低有关。需要进一步的研究来探索其潜在的机制及其对青光眼预防和治疗的意义。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。

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