Holstein A, Plaschke A, Hammer C, Egberts E-H
1st Department of Medicine, Klinikum Lippe-Detmold, Röntgenstrasse 18, 32756 Detmold, Germany.
Eur J Clin Pharmacol. 2003 Jun;59(2):91-7. doi: 10.1007/s00228-003-0592-4. Epub 2003 Apr 16.
To compare the clinical characteristics and time course of severe hypoglycaemia (SH) on glimepiride and the reference drug glibenclamide.
SH was defined as a symptomatic event requiring administration of i.v. glucose or of glucagon. Four hundred doctors working in acute care hospitals were randomly selected from the membership directory of the German Diabetes Association and sent a standardised questionnaire about sulphonylurea-induced SH that occurred between June 2001 and August 2002. Detailed data on history, medication, laboratory parameters, treatment and time course of the SH were analysed.
Altogether, 93 episodes of SH were registered, 37 on glimepiride and 56 on glibenclamide. The characteristics of the glimepiride- versus glibenclamide-induced SH were as follows: initial blood glucose 1.9+/-0.66 mmol/l versus 1.8+/-0.89 mmol/l, P=0.17; age 77+/-11.2 years versus 78+/-9.6 years, P=0.35; HbA1c 5.4+/-0.7% versus 5.2+/-0.9%, P=0.18; creatinine clearance 38+/-23 ml/min versus 54+/-32 ml/min, P=0.005; co-medication 6.2.+/-3 versus 3.6+/-3 preparations, P< 0.0001. Even very low doses of glimepiride (0.5 mg) and glibenclamide (0.88 mg) were associated with SH. Prolonged hypoglycaemia requiring more than 12 h i.v. glucose administration occurred in 8 of 37 of the glimepiride-treated subjects and 5 of 56 of those on glibenclamide. Prolonged hypoglycaemia necessitated infusion of 308+/-256 g (104-862 g) i.v. glucose over 43+/-16 h (24-64 h) in glimepiride-treated patients compared with 168+/-98 g (66-300 g) over 33+/-28 h (14-80 h) in glibenclamide-treated patients. Impaired renal function was present in 11 of 13 of all patients with prolonged hypoglycaemia and impaired liver function in 1 of 13.
In glimepiride- and glibenclamide-treated individuals with SH, no essential differences in the clinical characteristics or time course were shown; prolonged courses also occurred on glimepiride. Even in patients with only mild renal failure both preparations should be used with caution.
比较格列美脲与对照药物格列本脲所致严重低血糖（SH）的临床特征及病程。
SH定义为需要静脉注射葡萄糖或胰高血糖素的症状性事件。从德国糖尿病协会会员名录中随机选取400名在急症医院工作的医生，向他们发送一份关于2001年6月至2002年8月期间磺脲类药物所致SH的标准化问卷。分析有关SH的病史、用药、实验室参数、治疗及病程的详细数据。
共记录到93例SH事件，其中37例由格列美脲引起，56例由格列本脲引起。格列美脲与格列本脲所致SH的特征如下：初始血糖1.9±0.66 mmol/L对1.8±0.89 mmol/L，P = 0.17；年龄77±11.2岁对78±9.6岁，P = 0.35；糖化血红蛋白（HbA1c）5.4±0.7%对5.2±0.9%，P = 0.18；肌酐清除率38±23 ml/min对54±32 ml/min，P = 0.005；合并用药6.2±3种对3.6±3种制剂，P < 0.0001。即使是非常低剂量的格列美脲（0.5 mg）和格列本脲（0.88 mg）也与SH有关。在接受格列美脲治疗的37名受试者中有8例发生需要静脉输注葡萄糖超过12小时的持续性低血糖，接受格列本脲治疗的56名受试者中有5例发生。与接受格列本脲治疗的患者相比，接受格列美脲治疗的患者需要在43±16小时（24 - 64小时）内静脉输注308±256 g（104 - 862 g）葡萄糖，而接受格列本脲治疗的患者需要在33±28小时（14 - 80小时）内静脉输注168±98 g（66 - 300 g）葡萄糖。在所有发生持续性低血糖的患者中，13例中有11例存在肾功能损害，13例中有1例存在肝功能损害。
在接受格列美脲和格列本脲治疗发生SH的患者中，未显示出临床特征或病程有本质差异；格列美脲也会出现病程延长的情况。即使是仅患有轻度肾衰竭的患者，两种制剂均应谨慎使用。
