Mannucci Edoardo, Monami Matteo, Masotti Giulio, Marchionni Niccolò
Department of Critical Care Medicine and Surgery, Unit of Gerontology and Geriatrics, University of Florence, Florence, Italy.
Diabetes Metab Res Rev. 2004 Jan-Feb;20(1):44-7. doi: 10.1002/dmrr.411.
Increased mortality in diabetic patients treated with combinations of high doses of sulfonylureas and metformin was recently reported. This study was aimed at the assessment of mortality in patients treated with low-dose combinations of sulfonylureas and biguanides.
An observational cohort study was performed on a consecutive series of 927 outpatients with type 2 diabetes mellitus. Of these patients, 376 were treated with combinations of sulfonylureas (mean daily dose +/- SD: 7.3 +/- 3.2 mg for glibenclamide, and 338 +/- 79 mg for chlorpropamide) and biguanides (daily dose: 1.1 +/- 0.3 g for metformin, 60.1 +/- 19.6 mg for phenformin). Mortality was assessed through a search in the City of Florence Registry Office, with an average follow-up of 55.1 months.
After adjusting for other potential confounders (including age, duration of diabetes, BMI, hypertension, lipid profile, HbA1c, and insulin treatment), mortality was significantly higher in patients treated with combinations of sulfonylureas and biguanides than in the rest of the sample, (relative risk, RR: 2.08; 95% confidence interval, CI 1.18-3.67, and RR: 1.68; 95%CI 1.01-2.79 among women and men, respectively).
A higher mortality was observed in patients treated with combinations of sulfonylureas and biguanides, even at low doses. Safety of such combinations deserves further investigation.
最近有报道称，接受高剂量磺脲类药物与二甲双胍联合治疗的糖尿病患者死亡率增加。本研究旨在评估接受低剂量磺脲类药物与双胍类药物联合治疗患者的死亡率。
对连续927例2型糖尿病门诊患者进行了一项观察性队列研究。其中376例患者接受了磺脲类药物（格列本脲平均日剂量±标准差：7.3±3.2mg，氯磺丙脲为338±79mg）与双胍类药物（二甲双胍日剂量：1.1±0.3g，苯乙双胍为60.1±19.6mg）联合治疗。通过在佛罗伦萨市登记处查询评估死亡率，平均随访55.1个月。
在对其他潜在混杂因素（包括年龄、糖尿病病程、体重指数、高血压、血脂谱、糖化血红蛋白和胰岛素治疗）进行校正后，接受磺脲类药物与双胍类药物联合治疗的患者死亡率显著高于其余样本患者（相对风险，RR：2.08；95%置信区间，CI 1.18 - 3.67，女性和男性的RR分别为1.68；95%CI 1.01 - 2.79）。
即使是低剂量，接受磺脲类药物与双胍类药物联合治疗的患者死亡率也较高。此类联合用药的安全性值得进一步研究。
