Monami Matteo, Luzzi Chiara, Lamanna Caterina, Chiasserini Veronica, Addante Filomena, Desideri Carla Maria, Masotti Giulio, Marchionni Niccolò, Mannucci Edoardo
Department of Critical Care Medicine and Surgery, Unit of Gerontology and Geriatrics, University of Florence and Azienda Ospedaliera Vareggi, Via della Oblate 4, 50134 Florence, Italy.
Diabetes Metab Res Rev. 2006 Nov-Dec;22(6):477-82. doi: 10.1002/dmrr.642.
Several studies have shown an increase of mortality in diabetic patients treated with combinations of sulphonylureas and biguanides. Comparisons between different insulin secretagogues in combination with metformin with respect to all-cause mortality have not been reported so far.
An observational cohort study was performed on a consecutive series of 2002 outpatients with type 2 diabetes mellitus. Of these patients, 696 (34.8%) were receiving combinations of insulin secretagogues and biguanides at enrollment. Three-year mortality was assessed through research in the City of Florence Registry Office.
During follow-up, 295 deaths were recorded. Among patients on combined secretagogue and biguanide treatment, glibenclamide was associated with a significantly higher yearly mortality (8.7%) than repaglinide (3.1%; p = 0.002), gliclazide (2.1%; p = 0.001), and glimepiride (0.4%; p < 0.0001). After adjusting for potential confounders (including age; duration of diabetes; Body Mass Index (BMI); lipid profile; HbA(1c); insulin treatment; metformin doses; Charlson co-morbidity score; CCS), mortality remained significantly higher in patients treated with combinations of glibenclamide and metformin when compared to those treated with different insulin secretagogues (OR with 95% CI: 2.09 [1.07;4.11]).
In the present study, sulphonylureas with greater selectivity for beta-cell receptors, such as glimepiride and gliclazide, were associated with a lower mortality when used in combination with metformin in comparison with glibenclamide. Safety of such combinations deserves further investigation.
多项研究表明，使用磺脲类药物和双胍类药物联合治疗的糖尿病患者死亡率有所增加。迄今为止，尚未有关于不同胰岛素促泌剂与二甲双胍联合使用时全因死亡率的比较报道。
对连续纳入的2002例2型糖尿病门诊患者进行了一项观察性队列研究。其中，696例（34.8%）患者在入组时接受胰岛素促泌剂和双胍类药物联合治疗。通过在佛罗伦萨市登记处进行调查来评估三年死亡率。
在随访期间，记录到295例死亡。在接受促泌剂和双胍类药物联合治疗的患者中，格列本脲的年死亡率（8.7%）显著高于瑞格列奈（3.1%；p = 0.002）、格列齐特（2.1%；p = 0.001）和格列美脲（0.4%；p < 0.0001）。在对潜在混杂因素（包括年龄、糖尿病病程、体重指数（BMI）、血脂谱、糖化血红蛋白（HbA1c）、胰岛素治疗、二甲双胍剂量、查尔森合并症评分、CCS）进行调整后，与使用不同胰岛素促泌剂治疗相比，接受格列本脲和二甲双胍联合治疗的患者死亡率仍显著较高（OR及95%CI：2.09 [1.07；4.11]）。
在本研究中，与格列本脲相比，对β细胞受体具有更高选择性的磺脲类药物，如格列美脲和格列齐特，与二甲双胍联合使用时死亡率较低。此类联合用药的安全性值得进一步研究。
