Lin Yi-Cheng, Chen Chih-Wei, Huang Ling-Ya, Chen Bi-Li, Shao Yu-Hsuan Joni, Huang Chun-Yao
Department of Pharmacy, Taipei Medical University Hospital, Taipei, 11031, Taiwan.
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, 110, Taiwan.
Sci Rep. 2025 Aug 2;15(1):24852. doi: 10.1038/s41598-025-10215-7.
Research indicates a U-shaped association between mortality and glycated hemoglobin (HbA1c) levels in patients receiving sulfonylurea or insulin. However, the relationship between glucose levels and cardiovascular events in patients on novel agents with a lower hypoglycemic potential remains unknown. This study was aimed to examine the association between cardiovascular events and HbA1c in patients with type 2 diabetes receiving drugs with different hypoglycemic potentials. This is an observational cohort study using a multicenter electronic medical record database. This study included patients who received a diagnosis of type 2 diabetes between 2009 and 2020 and received non-insulin antidiabetic drugs. These drugs were divided into drugs with a high-hypoglycemic-risk (sulfonylurea and meglitinides) and drugs with a low-hypoglycemic-risk (incretin mimetics, sodium-glucose cotransporter-2 inhibitors, thiazolidinediones, and acarbose). The events of interest were mortality and major adverse cardiovascular events (MACEs). A total of 6,789 patients were included, with 3,191 patients in low-hypoglycemic-risk drugs cohort and 3,598 patients in high-hypoglycemic-risk drugs cohort. Both cohorts exhibited a U-shaped association between HbA1c levels and the risk of mortality and MACEs. Among patients receiving low-hypoglycemic-risk drugs, HbA1c levels of 6.7% and 6.8% were associated with the lowest risk of mortality and MACEs, respectively. Similarly, in patients receiving high-hypoglycemic-risk drugs, the lowest risk of mortality and MACEs was observed at HbA1c levels of 6.8% and 7.2%, respectively. Both low and high HbA1c levels were associated with an increased risk of mortality and cardiovascular events, whereas intermediate levels were linked to the lowest risk. These findings support a U-shaped association between glycemic control and adverse outcomes in patients with type 2 diabetes receiving non-insulin-based therapies.
研究表明，在接受磺脲类药物或胰岛素治疗的患者中，死亡率与糖化血红蛋白（HbA1c）水平呈U型关联。然而，在低血糖风险较低的新型药物治疗的患者中，血糖水平与心血管事件之间的关系仍不清楚。本研究旨在探讨接受不同降糖潜力药物治疗的2型糖尿病患者心血管事件与HbA1c之间的关联。这是一项使用多中心电子病历数据库的观察性队列研究。本研究纳入了2009年至2020年间被诊断为2型糖尿病并接受非胰岛素抗糖尿病药物治疗的患者。这些药物分为低血糖风险高的药物（磺脲类和格列奈类）和低血糖风险低的药物（胰高血糖素样肽-1类似物、钠-葡萄糖协同转运蛋白-2抑制剂、噻唑烷二酮类和阿卡波糖）。关注的事件是死亡率和主要不良心血管事件（MACE）。总共纳入了6789例患者，其中3191例患者在低血糖风险低的药物队列中，3598例患者在低血糖风险高的药物队列中。两个队列的HbA1c水平与死亡率和MACE风险之间均呈U型关联。在接受低血糖风险低的药物治疗的患者中，HbA1c水平分别为6.7%和6.8%时，死亡率和MACE风险最低。同样，在接受低血糖风险高的药物治疗的患者中，HbA1c水平分别为6.8%和7.2%时，死亡率和MACE风险最低。HbA1c水平过高和过低均与死亡率和心血管事件风险增加相关，而中等水平与最低风险相关。这些发现支持了接受非胰岛素治疗的2型糖尿病患者血糖控制与不良结局之间的U型关联。
