Pioglitazone use is known to be associated with a reduced risk of recurrent stroke in patients with diabetes mellitus (DM) who have a history of stroke. However, it is unclear whether this benefit extends to patients without a history of stroke. We aimed to evaluate the association between pioglitazone use and development of first attack of ischemic stroke in patients with newly diagnosed type 2 DM. Using longitudinal nationwide data from the 2002–2017 Korean National Health Insurance Service DM cohort, we analyzed the association between pioglitazone use and incidence of primary ischemic stroke using a nested case–control study. Among 128,171 patients with newly onset type 2 DM who were stroke-free at the time of DM diagnosis, 4796 cases of ischemic stroke were identified and matched to 23,980 controls based on age, sex, and the onset and duration of DM. The mean (standard deviation) follow-up time was 6.08 (3.34) years for the cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between ischemic stroke and pioglitazone use were analyzed by multivariable conditional logistic regression analyses adjusted for comorbidities, cardiometabolic risk profile, and other oral antidiabetic medications. Pioglitazone use was associated with a reduced risk of first attack of ischemic stroke (adjusted OR [AOR] 0.69, 95% CI 0.60–0.80) when compared with non-use. Notably, pioglitazone use was found to have a dose-dependent association with reduced rate of ischemic stroke emergence (first cumulative defined daily dose [cDDD] quartile AOR 0.99, 95% CI 0.74–1.32; second quartile, AOR 0.77, 95% CI 0.56–1.06; third quartile, AOR 0.51, 95% Cl 0.36–0.71; highest quartile, AOR 0.48, 95% CI 0.33–0.69). More pronounced risk reduction was found in patients who used pioglitazone for more than 2 years. A further stratified analysis revealed that pioglitazone use had greater protective effects in patients with risk factors for stroke, such as high blood pressure, obesity, and current smoking. Pioglitazone use may have a preventive effect on primary ischemic stroke in patients with type 2 DM, particularly in those at high risk of stroke.

中文翻译：

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使用吡格列酮与新发 2 型糖尿病患者缺血性卒中首次发作风险降低相关：一项全国性巢式病例对照研究

已知使用吡格列酮可以降低有中风病史的糖尿病 (DM) 患者中风复发的风险。然而，尚不清楚这种益处是否适用于没有中风病史的患者。我们旨在评估新诊断的 2 型 DM 患者使用吡格列酮与缺血性卒中首次发作之间的关联。使用来自 2002-2017 年韩国国民健康保险服务 DM 队列的纵向全国数据，我们使用嵌套病例对照研究分析了吡格列酮的使用与原发性缺血性卒中发生率之间的关联。在 128,171 名在 DM 诊断时无卒中的新发 2 型 DM 患者中，根据年龄、性别、以及 DM 的发作和持续时间。病例和对照的平均（标准偏差）随访时间为 6.08 (3.34) 年。缺血性卒中和吡格列酮使用之间关联的优势比 (OR) 和 95% 置信区间 (CI) 通过多变量条件逻辑回归分析进行分析，该分析针对合并症、心脏代谢风险概况和其他口服抗糖尿病药物进行了调整。与未使用吡格列酮相比，使用吡格列酮可降低缺血性卒中首次发作的风险（调整后 OR [AOR] 0.69，95% CI 0.60–0.80）。值得注意的是，发现吡格列酮的使用与缺血性卒中发生率降低呈剂量依赖性相关（第一个累积限定日剂量 [cDDD] 四分位数 AOR 0.99，95% CI 0.74–1.32；第二个四分位数，AOR 0.77，95% CI 0.56 –1.06；第三个四分位数，AOR 0.51，95% Cl 0。36–0.71；最高四分位数，AOR 0.48，95% CI 0.33–0.69）。在使用吡格列酮超过 2 年的患者中发现更明显的风险降低。进一步的分层分析显示，使用吡格列酮对具有中风危险因素（如高血压、肥胖和当前吸烟）的患者具有更大的保护作用。吡格列酮的使用可能对 2 型 DM 患者的原发性缺血性卒中具有预防作用，尤其是对卒中高危患者。