Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Department of Biostatistics, Yonsei University Graduate School of Public Health, Seoul, South Korea.
Cardiovasc Diabetol. 2021 Jul 27;20(1):152. doi: 10.1186/s12933-021-01339-x.
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.
已知吡格列酮的使用与曾有卒中史的糖尿病（DM）患者再次发生卒中的风险降低相关。然而，对于无卒中史的患者，其是否能从中获益尚不明确。我们旨在评估新诊断为 2 型 DM 的患者中，吡格列酮的使用与首发缺血性卒中之间的相关性。
利用 2002-2017 年韩国国家健康保险服务糖尿病队列的纵向全国数据，我们采用巢式病例对照研究，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系。在 128171 例无卒中史的初诊 2 型 DM 患者中，根据年龄、性别以及 DM 的发病和持续时间，共确定了 4796 例缺血性卒中病例，并匹配了 23980 例对照。病例和对照的中位（标准差）随访时间分别为 6.08（3.34）年。采用多变量条件逻辑回归分析，根据合并症、心血管代谢风险特征和其他口服降糖药物，调整了缺血性卒中与吡格列酮使用之间的比值比（OR）和 95%置信区间（CI）。
与未使用者相比，吡格列酮使用者首次发生缺血性卒中的风险降低（校正 OR [AOR]0.69，95%CI0.60-0.80）。值得注意的是，吡格列酮的使用与缺血性卒中发生率呈剂量依赖性相关（第 1 累积定义日剂量（cDDD）四分位 AOR0.99，95%CI0.74-1.32；第 2 四分位 AOR0.77，95%CI0.56-1.06；第 3 四分位 AOR0.51，95%CI0.36-0.71；第 4 四分位 AOR0.48，95%CI0.33-0.69）。使用吡格列酮超过 2 年的患者风险降低更为显著。进一步的分层分析显示，在有卒中危险因素（如高血压、肥胖和当前吸烟）的患者中，吡格列酮的使用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，尤其是在卒中风险较高的患者中。
