A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (UK Prospective Diabetes Study 44)
A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (UK Prospective Diabetes Study 44)
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DOI：
10.2337/diacare.22.6.960
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发表时间：
1999-06-01
期刊：
影响因子：
16.2
通讯作者：
Turner, RC
中科院分区：
文献类型：
--
作者：
Holman, RR;Cull, CA;Turner, RC
目的：确定a-葡萄糖苷酶抑制剂的独特作用模式，主要是降低餐后高血糖，为2型糖尿病的长期治疗提供了一种额外的治疗方法。研究设计和方法：我们研究了1946例患者（63%为男性），这些患者之前都参加了英国前瞻性糖尿病研究（UKPDS）。患者被随机分配到阿卡波糖组（n = 973），滴定到最大剂量100mg，每天3次，或匹配安慰剂组（n = 973）。平均+/- SD年龄为59 +/- 9岁，体重84 +/- 17 kg，糖尿病病程7.6 +/- 2.9年，中位（四分位数范围）HbA(1c) 7.9%(6.7-9.5)，空腹血糖（FPG） 8.7 mmol/l（6.8-11.1）。14%的患者单独接受饮食治疗，52%接受单一治疗，34%接受联合治疗。在UKPDS诊所每4个月监测患者3年。主要结局指标为HbA（1c）、FPG、体重、对研究药物的依从性、副作用发生率和主要临床事件发生频率。结果：在3年时，服用阿卡波糖的患者比例低于安慰剂（39比58%，P < 0.0001），不依从性的主要原因是肠胃胀气（30比12%，P < 0.0001）和腹泻（16比8%，P < 0.05）。意向治疗分析显示，与安慰剂相比，分配给阿卡波糖的患者在3年时的中位HbA（1c）显著降低0.2% （P < 0.001）。在继续接受分配治疗的患者中，3年的HbA（1c）差异（阿卡波糖309，安慰剂470）比中位HbA（1c）低0.5% （8.1 vs. 8.6%, P < 0.0001）。阿卡波糖除了单独给药外似乎同样有效；除了磺脲类、二甲双胍或胰岛素单药治疗外；或者结合更复杂的治疗方案。两组在FPG、体重、低血糖发生率或主要临床事件发生频率方面均无显著差异。结论：阿卡波糖在3年内显著改善了2型糖尿病患者的血糖控制，与糖尿病的合并治疗无关。阿卡波糖的谨慎滴定是必要的，因为已知的副作用会增加不依从率。
OBJECTIVE - To determine the degree to which a-glucosidase inhibitors, with their unique mode of action primarily reducing postprandial hyperglycemia, offer an additional therapeutic approach in the long-term treatment of type 2 diabetes.RESEARCH DESIGN AND METHODS - We studied 1,946 patients (63% men) who were previously enrolled in the U.K. Prospective Diabetes Study (UKPDS). The patients were randomized to acarbose (n = 973), titrating to a maximum dose of 100 mg three times per day, or to matching placebo (n = 973). Mean +/- SD age was 59 +/- 9 years, body weight 84 +/- 17 kg, diabetes duration 7.6 +/- 2.9 years, median (interquartile range) HbA(1c) 7.9% (6.7-9.5), and fasting plasma glucose (FPG) 8.7 mmol/l (6.8-11.1). Fourteen percent of patients were treated with diet alone, 52% with monotherapy, and 34% with combined therapy. Patients were monitored in UKPDS clinics every 4 months for 3 years. The main outcome measures were HbA(1c), FPG, body weight, compliance with study medication, incidence of side effects, and frequency of major clinical events.RESULTS - At 3 years, a lower proportion of patients were taking acarbose compared with placebo (39 vs. 58%, P < 0.0001), the main reasons for noncompliance being flatulence (30 vs. 12%, P < 0.0001) and diarrhea (16 vs. 8%, P < 0.05). Analysis by intention to treat showed that patients allocated to acarbose, compared with placebo, had 0.2% significantly lower median HbA(1c) at 3 years (P < 0.001). In patients remaining on their allocated therapy, the HbA(1c) difference at 3 years (309 acarbose, 470 placebo) was 0.5% lower median HbA(1c) (8.1 vs. 8.6%, P < 0.0001). Acarbose appeared to be equally efficacious when given in addition to diet alone; in addition to monotherapy with a sulfonylurea, metformin, or insulin; or in combination with more complex treatment regimens. No significant differences were seen in FPG, body weight, incidence of hypoglycemia, or frequency of major clinical events.CONCLUSIONS - Acarbose significantly improved glycemic control over 3 years in patients with established type 2 diabetes, irrespective of concomitant therapy for diabetes. Careful titration of acarbose is needed in view of the increased noncompliance rate seen secondary to the known side effects.