OBJECTIVE Sulfonylureas have been associated with an increased risk of cardiovascular adverse events and hypoglycemia, but it is unclear if these risks vary with different agents. We assessed whether the risks of acute myocardial infarction, ischemic stroke, cardiovascular death, all-cause mortality, and severe hypoglycemia differ between sulfonylureas grouped according to pancreas specificity and duration of action.

RESEARCH DESIGN AND METHODS Using the U.K. Clinical Practice Research Datalink, linked with the Hospital Episodes Statistics and the Office for National Statistics databases, we conducted a cohort study among patients with type 2 diabetes initiating monotherapy with sulfonylureas between 1998 and 2013. Adjusted hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, comparing use of pancreas-nonspecific, long-acting sulfonylureas (glyburide/glimepiride) to pancreas-specific, short-acting sulfonylureas (gliclazide/glipizide/tolbutamide).

RESULTS The cohort included 17,604 sulfonylurea initiators (mean [SD] follow-up 1.2 [1.5] years). Compared with specific, short-acting sulfonylureas (15,741 initiators), nonspecific, long-acting sulfonylureas (1,863 initiators) were not associated with an increased risk of acute myocardial infarction (HR 0.86; CI 0.55–1.34), ischemic stroke (HR 0.92; CI 0.59–1.45), cardiovascular death (HR 1.01; CI 0.72–1.40), or all-cause mortality (HR 0.81; CI 0.66–1.003), but with an increased risk of severe hypoglycemia (HR 2.83; CI 1.64–4.88).

CONCLUSIONS The nonspecific, long-acting sulfonylureas glyburide and glimepiride do not have an increased risk of cardiovascular adverse events compared with the specific, short-acting sulfonylureas gliclazide, glipizide, and tolbutamide. However, nonspecific, long-acting sulfonylureas glyburide and glimepiride have an increased risk of severe hypoglycemia.

目的磺脲类药物与心血管不良事件和低血糖的风险增加有关，但尚不清楚这些风险是否因不同药物而异。我们评估了根据胰腺特异性和作用持续时间分组的磺脲类药物在急性心肌梗塞，缺血性中风，心血管死亡，全因死亡率和严重低血糖的风险方面是否有所不同。

研究设计和方法使用英国临床实践研究数据链，与医院情节统计数据和国家统计局数据库相链接，我们对1998年至2013年间开始使用磺酰脲类单一疗法的2型糖尿病患者进行了队列研究。使用Cox比例风险模型估算了HRs和95％CI，比较了胰腺非特异性长效磺酰脲类（格列本脲/格列美脲）与胰腺特异性短效磺酰脲类（格列齐特/格列吡嗪/甲苯磺丁酰胺）的使用。

结果该队列包括17,604例磺脲类药物引发者（平均[SD]随访1.2 [1.5]年）。与特定的短效磺酰脲类药物（15,741个引发剂）相比，非特异性的长效磺酰脲类药物（1,863个引发剂）与急性心肌梗死（HR 0.86； CI 0.55–1.34），缺血性中风（HR 0.92； HR 0.52）无关。 CI 0.59–1.45），心血管死亡（HR 1.01； CI 0.72-1.40）或全因死亡率（HR 0.81； CI 0.66-1.003），但发生严重低血糖的风险增加（HR 2.83； CI 1.64–4.88） 。

结论与特异性短效磺酰脲类格列齐特，格列吡嗪和甲苯磺丁酰胺相比，非特异性长效磺酰脲类格列本脲和格列美脲不会增加心血管不良事件的风险。但是，非特异性，长效磺酰脲类格列本脲和格列美脲具有严重低血糖的风险增加。