Inzucchi Silvio E, Viscoli Catherine M, Young Lawrence H, Furie Karen L, Gorman Mark, Lovejoy Anne M, Dagogo-Jack Samuel, Ismail-Beigi Faramarz, Korytkowski Mary T, Pratley Richard E, Schwartz Gregory G, Kernan Walter N
Yale School of Medicine, New Haven, CT
Yale School of Medicine, New Haven, CT.
Diabetes Care. 2016 Oct;39(10):1684-92. doi: 10.2337/dc16-0798. Epub 2016 Jul 27.
The Insulin Resistance Intervention after Stroke (IRIS) trial recently found that pioglitazone reduced risk for stroke and myocardial infarction in patients with insulin resistance but without diabetes who had had a recent ischemic stroke or transient ischemic attack (TIA). This report provides detailed results on the metabolic effects of pioglitazone and the trial's prespecified secondary aim of diabetes prevention.
A total of 3,876 patients with recent ischemic stroke or TIA, no history of diabetes, fasting plasma glucose (FPG) <126 mg/dL, and insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) score >3.0 were randomly assigned to pioglitazone or placebo. Surveillance for diabetes onset during the trial was accomplished by periodic interviews and annual FPG testing.
At baseline, the mean FPG, HbA1c, insulin, and HOMA-IR were 98.2 mg/dL (5.46 mmol/L), 5.8% (40 mmol/mol), 22.4 μIU/mL, and 5.4, respectively. After 1 year, mean HOMA-IR and FPG decreased to 4.1 and 95.1 mg/dL (5.28 mmol/L) in the pioglitazone group and rose to 5.7 and 99.7 mg/dL (5.54 mmol/L), in the placebo group (all P < 0.0001). Over a median follow-up of 4.8 years, diabetes developed in 73 (3.8%) participants assigned to pioglitazone compared with 149 (7.7%) assigned to placebo (hazard ratio [HR] 0.48 [95% CI 0.33-0.69]; P < 0.0001). This effect was predominately driven by those with initial impaired fasting glucose (FPG >100 mg/dL [5.6 mmol/L]; HR 0.41 [95% CI 0.30-0.57]) or elevated HbA1c (>5.7% [39 mmol/mol]; HR 0.46 [0.34-0.62]).
Among patients with insulin resistance but without diabetes who had had a recent ischemic stroke or TIA, pioglitazone decreased the risk of diabetes while also reducing the risk of subsequent ischemic events. Pioglitazone is the first medication shown to prevent both progression to diabetes and major cardiovascular events as prespecified outcomes in a single trial.
中风后胰岛素抵抗干预（IRIS）试验最近发现，吡格列酮可降低近期发生缺血性中风或短暂性脑缺血发作（TIA）且有胰岛素抵抗但无糖尿病患者的中风和心肌梗死风险。本报告提供了吡格列酮代谢效应的详细结果以及该试验预先设定的预防糖尿病次要目标的结果。
共有3876例近期发生缺血性中风或TIA、无糖尿病病史、空腹血糖（FPG）<126mg/dL且通过胰岛素抵抗稳态模型评估（HOMA-IR）评分>3.0确定存在胰岛素抵抗的患者被随机分配至吡格列酮组或安慰剂组。通过定期访谈和年度FPG检测对试验期间糖尿病发病情况进行监测。
基线时，平均FPG、糖化血红蛋白（HbA1c）、胰岛素和HOMA-IR分别为98.2mg/dL（5.46mmol/L）、5.8%（40mmol/mol）、22.4μIU/mL和5.4。1年后，吡格列酮组的平均HOMA-IR和FPG分别降至4.1和95.1mg/dL（5.28mmol/L），而安慰剂组则升至5.7和99.7mg/dL（5.54mmol/L）（所有P<0.0001）。在中位随访4.8年期间，分配至吡格列酮组的73例（3.8%）参与者发生糖尿病，而分配至安慰剂组的有149例（7.7%）（风险比[HR]0.48[95%CI0.33-0.69]；P<0.0001）。这一效应主要由初始空腹血糖受损（FPG>100mg/dL[5.6mmol/L]；HR0.41[95%CI0.30-0.57]）或HbA1c升高（>5.7%[39mmol/mol]；HR0.46[0.34-0.62]）的患者驱动。
在近期发生缺血性中风或TIA且有胰岛素抵抗但无糖尿病的患者中，吡格列酮降低了糖尿病风险，同时也降低了后续缺血性事件的风险。吡格列酮是首个在单一试验中被证明可预防进展为糖尿病和主要心血管事件这两个预先设定结局的药物。
