Department of Internal Medicine, District Hospital, Kronach, Germany.
Clin Drug Investig. 2003;23(10):679-86. doi: 10.2165/00044011-200323100-00007.
Multiple oral therapies are required long term for the majority of patients with type 2 diabetes mellitus to achieve acceptable glycaemic levels; alternatively, insulin therapy has to be initiated. This study investigated the addition of acarbose to maximum doses of sulfonylurea in very poorly controlled type 2 diabetes patients and assessed its effect in delaying further glycaemic deterioration.
In this 78-week, double-blind, placebo-controlled European study, patients were randomised to receive acarbose, titrated to a maximum dose of 100mg three times daily, or matching placebo. Concomitant sulfonylurea treatment (glibenclamide/gliclazide) was to remain unchanged throughout the study. A sample size of 171 patients per treatment arm was calculated. The primary efficacy analysis was intention to treat.
The change in glycosylated haemoglobin (HbA(1c)) levels from baseline to the end of the study was regarded as the primary efficacy variable. Patients whose HbA(1c) levels increased above 10.5% on two consecutive visits terminated the study prematurely because of insulin administration. Secondary efficacy variables included the changes in blood glucose and C-peptide, both at fasting and at the 1h-postprandial level.
A total of 330 patients (acarbose 164, placebo 166) were valid for the efficacy analysis. Patients were generally overweight (body mass index 29.0 kg/m(2)) and showed very poor metabolic control (HbA(1c) >9%, fasting blood glucose >200 mg/dL, and 1h-postprandial blood glucose >300 mg/dL).
Acarbose significantly improved HbA(1c) levels compared with placebo (least square mean [LS-mean] difference -0.54%, 95% CI -0.86 to -0.22; p = 0.001). A number of patients had to discontinue the study prematurely because of insulin administration (24.5% in the placebo and 14.2% in the acarbose group). There was a significant LS-mean difference of -14.8 mg/dL (p = 0.0195) in fasting blood glucose levels and highly significant differences in 1h-postprandial blood glucose (LS-mean difference -33.4 mg/dL, p < 0.0001) and in the rise in blood glucose from fasting to 1h-postprandial (LS-mean difference -19.6 mg/dL, p = 0.0001), all in favour of acarbose. Acarbose was shown to have a good safety profile and was generally well tolerated.
Acarbose was shown to have the potential to delay further deterioration of glucose control in type 2 diabetes patients who are very poorly controlled with maximum sulfonylurea doses.
对于大多数 2 型糖尿病患者来说，需要长期使用多种口服药物才能达到可接受的血糖水平；或者，必须开始胰岛素治疗。本研究旨在探讨阿卡波糖添加到磺酰脲类药物最大剂量治疗血糖控制极差的 2 型糖尿病患者的效果，并评估其延缓血糖恶化的作用。
这是一项为期 78 周的、双盲、安慰剂对照的欧洲研究，患者被随机分配接受阿卡波糖治疗，滴定至最大剂量 100mg，每日 3 次，或接受匹配的安慰剂。整个研究期间，磺酰脲类药物（格列本脲/格列齐特）治疗保持不变。计算出每组 171 名患者的样本量。主要疗效分析采用意向治疗。
从基线到研究结束时糖化血红蛋白（HbA1c）水平的变化被视为主要疗效变量。两次连续就诊时 HbA1c 水平升高超过 10.5%的患者提前终止研究，因为开始使用胰岛素。次要疗效变量包括空腹和餐后 1 小时血糖的变化。
共有 330 名患者（阿卡波糖 164 名，安慰剂 166 名）符合疗效分析的条件。患者通常超重（体重指数 29.0kg/m2），代谢控制极差（HbA1c>9%，空腹血糖>200mg/dL，餐后 1 小时血糖>300mg/dL）。
阿卡波糖与安慰剂相比，显著改善了 HbA1c 水平（最小二乘均数[LS-均值]差异-0.54%，95%置信区间-0.86 至-0.22；p=0.001）。由于胰岛素治疗，许多患者不得不提前终止研究（安慰剂组 24.5%，阿卡波糖组 14.2%）。空腹血糖的 LS-均值差异有统计学意义（-14.8mg/dL，p=0.0195），餐后 1 小时血糖差异具有高度统计学意义（LS-均值差异-33.4mg/dL，p<0.0001），从空腹到餐后 1 小时血糖升高差异也有统计学意义（LS-均值差异-19.6mg/dL，p=0.0001），所有这些都有利于阿卡波糖。阿卡波糖具有良好的安全性，总体耐受性良好。
阿卡波糖具有延缓血糖控制极差的 2 型糖尿病患者血糖进一步恶化的潜力，这些患者接受磺酰脲类药物最大剂量治疗。
