Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes
Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes
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DOI：
10.2337/diacare.27.11.2628
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发表时间：
2004-11-01
期刊：
影响因子：
16.2
通讯作者：
Baron, AD
中科院分区：
文献类型：
--
作者：
Buse, JB;Henry, RR;Baron, AD
研究设计与方法--这是一项在美国101个地点进行的为期30周的三盲、安慰剂对照研究。经过4周、单盲、安慰剂引导期后，377名受试者被随机分配(60%的男性，年龄55+/-11岁，BMI 33+/-6 kg/m(2)，8.6+/-1.2%[+/-SD])，开始4周，每天两次皮下注射艾塞那肽5杯(早餐和晚餐前；手臂A和B)或安慰剂。随后，手臂B的受试者被升级到10杯b.i.d。埃克塞那肽。结果：30周时，服用10杯、5杯和安慰剂组患者的糖化血红蛋白(1c)较基线分别为-0.86+/-0.11、-0.46+/-0.12和0.12+/-0.09%(+/-SE)(调整后P<；0.001)。在基线为HbA(1c)和Gt的可评估受试者中，7%(n=237%)、41%(10ug)、33%(5ug)和9%(安慰剂)的HbA(1c)小于或等于7%(P<；0.001)。与安慰剂组相比，10杯组的空腹血糖浓度降低(P<；0.05)。服用艾塞那肽的受试者有剂量依赖性的渐进性体重减轻，在研究结束时，服用10杯艾塞那肽的受试者体重比基线减少了1.6+/-0.3公斤(P<；0.05与安慰剂相比)。最常见的不良反应一般为轻度或中度的胃肠道反应。没有观察到严重的低血糖。结论在未能达到最大有效剂量磺脲类药物的2型糖尿病患者中，埃塞那肽显著降低了HBA(1c)。艾塞那肽总体耐受性良好，7d与体重减轻有关。
OBJECTIVE- This study evaluated the ability of the incretin mimetic exenatide (exendin-4) to improve glycemic control in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy.RESEARCH DESIGN AND METHODS- This was a triple-blind, placebo-controlled, 30-week study conducted at 101 sites in the U.S. After a 4-week, single-blind, placebo lead-in period, 377 subjects were randomized (60% men, age 55 +/- 11 years, BMI 33 +/- 6 kg/m(2), 8.6 +/- 1.2% [+/-SD]) and began 4 weeks at 5 mug subcutaneous exenatide twice daily (before breakfast and dinner; arms A and B) or placebo. Subsequently, subjects in arm B were escalated to 10 mug b.i.d. exenatide. All subjects continued sulfonylurea therapy.RESULTS- At week 30, HbA(1c) changes from baseline were -0.86 +/- 0.11, -0.46 +/- 0.12, and 0.12 +/- 0.09% (+/-SE) in the 10-mug, 5-mug, and placebo arms, respectively (adjusted P < 0.001). Of evaluable subjects with baseline HbA(1c) > 7% (n = 237), 41% (10 mug), 33% (5 mug), and 9% (placebo) achieved HbA(1c) less than or equal to 7% (P < 0.001). Fasting plasma glucose concentrations decreased in the 10-mug arm compared with placebo (P < 0.05). Subjects in the exenatide arms had dose-dependent progressive weight loss, with an end-of-study loss in the 10-mug exenatide arm of -1.6 +/- 0.3 kg from baseline (P < 0.05 vs. placebo). The most frequent adverse events were generally mild or moderate and gastrointestinal in nature. No severe hypoglycemia was observed.CONCLUSIONS- Exenatide significantly reduced HbA(1c) in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea. Exenatide was generally well tolerated and was associate7d with weight loss.