Turchin Alexander, Petito Lucia C, Hegermiller Emma, Carnahan Ryan, DeVries Andrea, Goel Satyender, Lansang M Cecilia, McDonnell Marie E, Nair Vinit, Priest Elisa, Willey Vincent J, Kaul Alan F, Hernán Miguel A
Division of Endocrinology, Brigham and Women's Hospital, Boston, Massachusetts.
Harvard Medical School, Boston, Massachusetts.
JAMA Netw Open. 2025 Jul 1;8(7):e2523067. doi: 10.1001/jamanetworkopen.2025.23067.
Sulfonylureas are commonly used to treat type 2 diabetes (T2D). Research findings on cardiovascular risk associated with sulfonylureas have been inconsistent.
To emulate a target trial that compares the risk of cardiovascular events after initiation of treatment with individual sulfonylureas or dipeptidyl peptidase 4 inhibitors (DPP4is).
DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness research study included individuals with T2D and moderate cardiovascular risk treated with metformin monotherapy who received care at 1 of 10 US health systems or were insured by 1 of 2 large health insurance plans between January 1, 2014, and January 1, 2023. Data were analyzed from July 2024 to March 2025.
Initiation of treatment with a sulfonylurea (glimepiride, glipizide, or glyburide) or a DPP4i (reference category) as a second line therapy after metformin.
The primary outcome was a 4-point composite of major adverse cardiovascular events (MACE-4): myocardial infarction, ischemic stroke, heart failure hospitalization, or cardiovascular death (from any of these conditions). The 5-year risks of each outcome were estimated.
Among 48 165 eligible individuals (median [IQR] age, 61 [52-69] years; 22 674 female [47.1%]; median [IQR] hemoglobin A1C, 7.8% [7.3%-8.5%]; median [IQR] low-density lipoprotein cholesterol, 89 mg/dL [70-112 mg/dL]), 18 147 started glipizide, 14 282 started glimepiride, 1887 started glyburide, and 13 849 started a DPP4i. Over the median (IQR) follow-up of 37 (20-64) months, 3158 individuals (6.6%) experienced a MACE-4. The estimated 5-year risks of MACE-4 were 8.1% (95% CI, 7.5%-8.7%) for DPP4i, 8.4% (95% CI, 6.8%-9.9%) for glyburide, 8.6% (95% CI, 7.9%-9.2%) for glimepiride, and 9.1% (95% CI, 8.7%-9.7%) for glipizide. Compared with DPP4is, the 5-year risk ratio of MACE-4 was 1.13 (95% CI, 1.03-1.23) for glipizide, 1.07 (95% CI, 0.96-1.16) for glimepiride, and 1.04 (95% CI, 0.83-1.24) for glyburide.
In this comparative effectiveness research study of sulfonylureas vs DPP4i in patients with T2D, the risk of MACE-4 events was highest for glipizide. These findings suggest that sulfonylureas, glipizide in particular, may not be the optimal agent in treatment of individuals with T2D at moderate cardiovascular risk.
磺脲类药物常用于治疗2型糖尿病（T2D）。关于磺脲类药物相关心血管风险的研究结果并不一致。
模拟一项目标试验，比较起始使用个别磺脲类药物或二肽基肽酶4抑制剂（DPP4i）治疗后心血管事件的风险。
设计、设置和参与者：这项比较有效性研究纳入了接受二甲双胍单药治疗且有中度心血管风险的T2D患者，这些患者于2014年1月1日至2023年1月1日期间在美国10个医疗系统之一接受治疗或由2个大型健康保险计划之一承保。数据于2024年7月至2025年3月进行分析。
在二甲双胍治疗后，起始使用磺脲类药物（格列美脲、格列吡嗪或格列本脲）或DPP4i（参照类别）作为二线治疗。
主要结局是主要不良心血管事件（MACE-4）的4点复合指标：心肌梗死、缺血性中风、心力衰竭住院或心血管死亡（由上述任何一种情况导致）。估计了每种结局的5年风险。
在48165名符合条件的个体中（年龄中位数[四分位间距]为61[52 - 69]岁；女性22674名[47.1%]；血红蛋白A1C中位数[四分位间距]为7.8%[7.3% - 8.5%]；低密度脂蛋白胆固醇中位数[四分位间距]为89mg/dL[70 - 112mg/dL]），18147人起始使用格列吡嗪，14282人起始使用格列美脲，1887人起始使用格列本脲，13849人起始使用DPP4i。在中位（四分位间距）随访37（20 - 64）个月期间，3158名个体（6.6%）发生了MACE-4。DPP4i的MACE-4估计5年风险为8.1%（95%置信区间，7.5% - 8.7%），格列本脲为8.4%（95%置信区间，6.8% - 9.9%），格列美脲为8.6%（95%置信区间，7.9% - 9.2%），格列吡嗪为9.1%（95%置信区间，8.7% - 9.7%）。与DPP4i相比，格列吡嗪的MACE-4 5年风险比为1.13（95%置信区间，1.03 - 1.23），格列美脲为1.07（95%置信区间，0.96 - 1.16），格列本脲为1.04（95%置信区间，0.83 - 1.24）。
在这项针对T2D患者比较磺脲类药物与DPP4i的比较有效性研究中，格列吡嗪的MACE-4事件风险最高。这些发现表明，磺脲类药物，尤其是格列吡嗪，可能不是治疗中度心血管风险T2D个体的最佳药物。
