University College London Medical School and Royal Free Hospital School of Medicine, Joint Department of Medicine, Whittington Hospital, London, England.
Clin Drug Investig. 1998;16(4):303-17. doi: 10.2165/00044011-199816040-00005.
This study aimed to compare the effects of glimepiride and glibenclamide on glycaemic control and a range of risk factors for ischaemic heart disease (IHD), including concentrations of insulin-like molecules.
A double-blind, placebo-controlled, randomised, crossover comparison of 4 weeks of treatment with glibenclamide 2.5 to 20 mg/day and glimepiride 1 to 8 mg/day was undertaken in 29 type 2 (non-insulin-dependent) diabetic patients. The average (mean +/- SD) duration of diabetes was 8.5 (+/- 5.9) years.
Compared with placebo, fasting plasma glucose was significantly lower on both drugs [placebo (P): mean (SD) 11.9 (3.3) mmol/L, glibenclamide: 9.5 (3.2); p < 0.0005, glimepiride: 10.6 (3.4); p = 0.01] and lower on glibenclamide than glimepiride (p = 0.003). The integrated, meal-stimulated rise in glucose was lower with glimepiride, but not glibenclamide, compared with placebo [P: 588.1 (372.2) mmol/L.min, glimepiride: 443.0 (346.9) mmol/L.min; p = 0.010, glibenclamide: 586.4 (366.2) mmol/L.min; p = 0.630]. There was no between-drug difference (p = 0.145). Fasting insulin did not differ compared with placebo [P: 92.3 (61.3) pmol/L, glimepiride: 91.8 (60.6) pmol/L; p = 0.787, glibenclamide: 87.8 (51.6) pmol/L; p = 0.379] and there was no between-drug difference (p = 0.601). There were no significant differences in effect upon fasting concentrations of C-peptide, proinsulin, des 31,32 proinsulin or the ratio of proinsulin-like to total insulin-like molecules. The integrated insulin and C-peptide responses to a meal were significantly greater on both drugs than on placebo [insulin: median (25th, 75th percentile), P: 7073 (2430-18296) pmol/L.min, glibenclamide: 18045 (4290-35850) pmol/L.min; p = 0.0005, glimepiride: 14355 (5880-32820) pmol/L.min; p = 0.0001; C-peptide mean (SD): P: 51.89 (49.01) nmol/L.min, glibenclamide: 90.15 (59.44) nmol/L.min; p = 0.006, glimepiride: 89.75 (61.78) nmol/L.min; p = 0.007], but there was no between-drug difference [integrated insulin (p = 0.923), integrated C-peptide (p = 0.680)]. Compared with placebo, plasminogen activator inhibitor (PAI) antigen was significantly lower on glibenclamide but not glimepiride [P: 28.8 (19.7) microg/L, glimepiride: 24.4 (15.2) microg/L; p = 0.300, glibenclamide: 20.0 (10.9) microg/L; p = 0.003]. PAI activity was similar with all agents, as was low density lipoprotein (LDL)-cholesterol [P: 4.4 (1.2) mmol/L, glimepiride: 4.2 (0.9) mmol/L; p = 0.225, glibenclamide: 4.5 (1.4) mmol/L; p = 0.174]. Corrected for fasting plasma glucose, LDL was 0.5 mmol/L lower on glimepiride than on glibenclamide (95% confidence interval: -0.8, -0.2), a clinically significant difference. There were no significant differences in other measured factors.
Both drugs improved glycaemia without adversely affecting a range of IHD risk factors.
本研究旨在比较格列美脲和格列本脲对血糖控制和一系列缺血性心脏病（IHD）风险因素的影响，包括胰岛素样分子的浓度。
对 29 例 2 型（非胰岛素依赖型）糖尿病患者进行了为期 4 周的双盲、安慰剂对照、随机交叉比较，分别接受格列本脲 2.5 至 20mg/天和格列美脲 1 至 8mg/天的治疗。糖尿病的平均（均数±标准差）病程为 8.5（±5.9）年。
与安慰剂相比，两种药物均使空腹血糖明显降低[安慰剂（P）：平均（SD）11.9（3.3）mmol/L，格列本脲：9.5（3.2）；p<0.0005，格列美脲：10.6（3.4）；p=0.01]，且格列美脲较格列本脲更低（p=0.003）。与安慰剂相比，格列美脲使餐后血糖刺激的葡萄糖整体升高幅度降低，但格列本脲无此作用[P：588.1（372.2）mmol/L.min，格列美脲：443.0（346.9）mmol/L.min；p=0.010，格列本脲：586.4（366.2）mmol/L.min；p=0.630]。药物之间无差异（p=0.145）。与安慰剂相比，空腹胰岛素无差异[P：92.3（61.3）pmol/L，格列美脲：91.8（60.6）pmol/L；p=0.787，格列本脲：87.8（51.6）pmol/L；p=0.379]，且药物之间无差异（p=0.601）。空腹 C 肽、前胰岛素、去 31、32 前胰岛素或胰岛素样分子与总胰岛素样分子的比例无显著差异。与安慰剂相比，两种药物餐后胰岛素和 C 肽的综合反应均显著增加[胰岛素：中位数（25%，75%分位数），P：7073（2430-18296）pmol/L.min，格列本脲：18045（4290-35850）pmol/L.min；p=0.0005，格列美脲：14355（5880-32820）pmol/L.min；p=0.0001；C 肽平均（SD），P：51.89（49.01）nmol/L.min，格列本脲：90.15（59.44）nmol/L.min；p=0.006，格列美脲：89.75（61.78）nmol/L.min；p=0.007]，但药物之间无差异[综合胰岛素（p=0.923），综合 C 肽（p=0.680）]。与安慰剂相比，格列本脲使纤溶酶原激活物抑制剂（PAI）抗原显著降低，但格列美脲无此作用[P：28.8（19.7）μg/L，格列美脲：24.4（15.2）μg/L；p=0.300，格列本脲：20.0（10.9）μg/L；p=0.003]。PAI 活性与所有药物相似，低密度脂蛋白（LDL）-胆固醇也相似[P：4.4（1.2）mmol/L，格列美脲：4.2（0.9）mmol/L；p=0.225，格列本脲：4.5（1.4）mmol/L；p=0.174]。校正空腹血糖后，格列美脲使 LDL 比格列本脲低 0.5mmol/L（95%置信区间：-0.8，-0.2），这是一个有临床意义的差异。其他测量因素无显著差异。
两种药物均改善了血糖，且不影响一系列 IHD 风险因素。
