Riddle Matthew C, Henry Robert R, Poon Terri H, Zhang Bei, Mac Susanna M, Holcombe John H, Kim Dennis D, Maggs David G
Oregon Health & Sciences University, Portland, OR, USA.
Diabetes Metab Res Rev. 2006 Nov-Dec;22(6):483-91. doi: 10.1002/dmrr.646.
In two placebo-controlled 30-week trials, treatment with exenatide reduced HbA(1c) and body weight in patients with type 2 diabetes in the context of sulphonylurea (SU) or SU plus metformin (MET) as background treatment. This analysis examines the effects of 82 weeks of exenatide treatment for participants in these earlier 30-week trials.
Data were pooled from the two pivotal trials of exenatide added to SU or SU plus MET. Both 30-week, placebo-controlled trials of 5 microg or 10 microg exenatide b.i.d. were followed by 52-week open-label, uncontrolled extension studies in which all participants received 10 microg exenatide b.i.d. and continued prior oral therapies. This interim analysis includes data for 222 patients who completed 82 weeks of exenatide treatment (61% M, age 57 +/- 10 y, weight 99 +/- 21 kg, BMI 34 +/- 6 kg/m(2), HbA(1c)8.4 +/- 1.0% [mean +/- SD]).
Reduction in HbA(1c) from baseline to week 30 (-0.8 +/- 0.1% and -1.0 +/- 0.1% for 5 microg b.i.d. and 10 microg b.i.d., respectively [mean +/- SE]) was sustained up to week 82 (-1.0 +/- 0.1%). Of 207 patients with baseline HbA(1c) > 7%, 44% achieved HbA(1c) < or = 7% at week 82. Reduction of body weight from baseline to week 30 (-1.4 +/- 0.3 kg and -2.1 +/- 0.3 kg for 5 microg b.i.d. and 10 microg b.i.d., respectively) was progressive up to week 82 (-4.0 +/- 0.3 kg). The most frequent adverse events were nausea and hypoglycaemia, both generally mild to moderate in intensity.
Exenatide added to maximally effective doses of SU or SU plus MET resulted in a sustained reduction in HbA(1c) and a progressive reduction in weight over 1 1/2 years.
在两项为期30周的安慰剂对照试验中，以磺脲类药物（SU）或SU加二甲双胍（MET）作为背景治疗，艾塞那肽治疗可降低2型糖尿病患者的糖化血红蛋白（HbA₁c）水平和体重。本分析旨在研究在这些早期30周试验中的参与者接受82周艾塞那肽治疗的效果。
汇总两项将艾塞那肽添加到SU或SU加MET中的关键试验的数据。两项为期30周、安慰剂对照的试验，分别给予5微克或10微克艾塞那肽每日两次，随后进行为期52周的开放标签、非对照延长期研究，所有参与者均接受10微克艾塞那肽每日两次，并继续之前的口服治疗。本次中期分析纳入了222例完成82周艾塞那肽治疗的患者的数据（男性占61%，年龄57±10岁，体重99±21千克，体重指数34±6千克/米²，HbA₁c 8.4±1.0% [均值±标准差]）。
从基线到第30周HbA₁c的降低幅度（5微克每日两次组为-0.8±0.1%，10微克每日两次组为-1.0±0.1% [均值±标准误]）在第82周时仍持续存在（-1.0±0.1%）。在207例基线HbA₁c>7%的患者中，44%在第82周时HbA₁c≤7%。从基线到第30周的体重减轻幅度（5微克每日两次组为-1.4±0.3千克，10微克每日两次组为-2.1±0.3千克）在第82周时逐渐增加（-4.0±0.3千克）。最常见的不良事件是恶心和低血糖，两者强度一般为轻度至中度。
在最大有效剂量的SU或SU加MET基础上加用艾塞那肽，可使HbA₁c持续降低，并在1年半的时间里使体重逐渐减轻。
