PURPOSE Pleiotropic cardiovascular benefits of sodium glucose co-transporter 2 inhibitors (SGLT2i) have been demonstrated in patients with type 2 diabetes mellitus due to vascular remodeling effects. It is unclear whether a similar benefit may be seen for glaucoma. The purpose of this study is to assess the effect of SGLT2i on the risk of glaucoma in patients with type 2 diabetes. DESIGN Target trial emulation using a population-based, propensity score-matched clinical cohort approach. METHODS Setting: Population-based, propensity score-matched clinical cohort study. STUDY POPULATION Adults with type 2 diabetes in the United States who newly initiated treatment with SGLT2i, dipeptidyl peptidase 4 inhibitors (DPP4i), or glucagon-like peptide-1 receptor agonists (GLP1RA) between 2013 and 2023. After propensity score matching, 722,446 patients were included in the SGLT2i arm and the DPP4i arm, respectively. Participants were matched based on age at index, race and sex, comorbidities, and concomitant use of medications. EXPOSURE Treatment with SGLT2i for type 2 diabetes. MAIN OUTCOME MEASURE(S) Incidence of new-onset glaucoma and its subtypes after initiation of SGLT2i, DPP4i, or GLP1RA. Subgroup analyses were performed to demonstrate the effect of individual SGLT2i on incident glaucoma. RESULTS Patients on SGLT2i compared to those on DPP4 had a lower risk of glaucoma (HR: 0.815, 95% confidence interval [CI]: 0.794, 0.837), including open-angle glaucoma (HR: 0.755, 95%CI: 0.729, 0.781) and primary angle-closure glaucoma (HR: 0.592, 95%CI: 0.540, 0.650). Among all SGLT2i, ertugliflozin (HR: 0.668, 95%CI: 0.512, 0.871) was associated with the lowest risk of glaucoma, followed by empagliflozin (HR: 0.727, 95%CI: 0.696, 0.759), then dapagliflozin (HR: 0.814, 95%CI: 0.774, 0.855). The protective effect of SGLT2i on glaucoma was validated when compared with GLP1RA (HR: 0.932, 95%CI: 0.906, 0.959). CONCLUSIONS Patients on SGLT2i, especially ertugliflozin and empagliflozin, had a significantly lower risk of incident glaucoma compared to those on DPP4i, an association that was less robust but significant in a sensitivity analysis using GLP1RA as the active comparator. SGLT2i had a protective effect for both open-angle glaucoma and angle-closure glaucoma.

中文翻译：

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钠-葡萄糖协同转运蛋白 2 抑制剂和 2 型糖尿病患者的青光眼。


目的 由于血管重塑作用，钠葡萄糖协同转运蛋白 2 抑制剂 （SGLT2i） 的多效性心血管益处已在 2 型糖尿病患者中得到证实。目前尚不清楚青光眼是否可能看到类似的益处。本研究的目的是评估 SGLT2i 对 2 型糖尿病患者青光眼风险的影响。设计 使用基于人群的倾向评分匹配的临床队列方法进行目标试验模拟。方法 设置： 基于人群的、倾向评分匹配的临床队列研究。研究人群 2013 年至 2023 年间新开始使用 SGLT2i、二肽基肽酶 4 抑制剂 （DPP4i） 或胰高血糖素样肽-1 受体激动剂 （GLP1RA） 治疗的美国 2 型糖尿病成人患者。倾向评分匹配后，SGLT2i 组和 DPP4i 组分别纳入 722,446 例患者。参与者根据指数年龄、种族和性别、合并症和伴随药物使用进行匹配。暴露 使用 SGLT2i 治疗 2 型糖尿病。主要结局指标 SGLT2i、DPP4i 或 GLP1RA 开始后新发青光眼及其亚型的发生率。进行亚组分析以证明个体 SGLT2i 对新发青光眼的影响。结果 与 DPP4 组患者相比，SGLT2i 组患者患青光眼的风险较低 （HR： 0.815， 95% 置信区间 [CI]： 0.794， 0.837），包括开角型青光眼 （HR： 0.755， 95%CI： 0.729， 0.781） 和原发性闭角型青光眼 （HR： 0.592， 95%CI： 0.540， 0.650）。在所有 SGLT2i 中，厄格列净 （HR： 0.668， 95%CI： 0.512， 0.871） 与青光眼风险最低相关，其次是恩格列净 （HR： 0.727， 95%CI： 0.696， 0.759），然后是达格列净 （HR： 0.814， 95%CI： 0.774， 0.与 GLP1RA 相比，SGLT2i 对青光眼的保护作用得到验证 （HR： 0.932， 95%CI： 0.906， 0.959）。结论 与 DPP4i 患者相比，SGLT2i 患者，尤其是厄格列净和恩格列净患者发生青光眼的风险显著降低，这种关联不太可靠，但在使用 GLP1RA 作为活性对照的敏感性分析中具有显著意义。SGLT2i 对开角型青光眼和闭角型青光眼均具有保护作用。