Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes
Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes
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DOI：
10.1016/j.clinthera.2006.10.020
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发表时间：
2006-10-01
影响因子：
3.2
通讯作者：
Thorsteinsson, Birger
中科院分区：
文献类型：
--
作者：
Philis-Tsimikas, Athena;Charpentier, Guillaume;Thorsteinsson, Birger
背景资料：许多控制不佳的2型糖尿病（DM）患者接受初始胰岛素治疗时，在现有口服降糖药物（OAD）治疗方案中添加基础制剂。以这种方式使用，胰岛素类似物地特胰岛素与改善血糖控制相关，其幅度类似于中性鱼精蛋白哈格多恩（NPH），低血糖和体重增加的发生率较低。最初的研究调查了地特给药BID，但药理学数据表明，地特可能是有效的QD administration.Objectives：本研究的目的是比较的有效性和耐受性的地特与NPH管理QD与>= 1 OAD在控制不佳的2型DM，并比较不同的给药时间地特。这项为期20周的多中心、随机、开放标签、3组、平行组试验在欧洲和美国的91家中心进行。如果年龄≥ 18岁，体重指数（BMI）= 1 OAD，则男性和女性有资格参与。患者被随机分配接受地特胰岛素晚间SC注射、地特胰岛素早餐前注射或NPH胰岛素晚间注射（1：1：1），初始剂量为10 IU（U）。（285名男性，219名女性;平均[SD]年龄，59 [11]岁;平均[SD] BMI，30 [5] kg/m（2）;早餐前地特胰岛素，168;晚上地特胰岛素，170; NPH晚上胰岛素，166）。意向治疗人群包括498例患者。早晨和晚上地特米尔与HbA（1c）降低相关，与晚上NPH相似（原始平均降低分别为-1.58%、-1.48%和-1.74%）。九点血糖曲线和空腹及餐前血糖数据发现，与晚间方案相比，早晨地特米与不同的昼夜血糖曲线相关。与夜间NPH相比，使用夜间地特米后，24小时和夜间低血糖分别减少了53%（P = 0.019）和65%（P = 0.031）。低血糖发生率在晨间和晚间接受地特米尔的两组之间没有显著差异，但晨间地特米尔与晚间NPH相比，夜间低血糖进一步减少了87%（P < 0.001）。早晨地特、晚上地特和NPH组的体重分别增加1.2、0.7和1.6 kg（晚上地特vs NPH组P = 0.005）。在其他耐受性endpoints.Conclusions：2型糖尿病控制不佳的患者中，>= 1 OAD的本研究结果表明，地特胰岛素QD在早晨或晚上可用于改善血糖控制。与NPH相比，地特胰岛素在这一作用中可能具有一些耐受性优势。
Background: Many patients with poorly controlled type 2 diabetes mellitus (DM) receive, as initial insulin treatment, the addition of a basal formulation to an existing regimen of oral antidiabetic drug (OAD) therapy. Used this way, the insulin analogue detemir has been associated with improved glycemic control of a magnitude similar to neutral protamine Hagedorn (NPH), with lower rates of hypoglycemia and weight gain. Initial studies investigated detemir administered BID, but pharmacologic data suggest that detemir might be effective with QD administration.Objectives: The alms of this study were to compare the effectiveness and tolerability of detemir versus NPH administered QD together with >= 1 OAD in poorly controlled type 2 DM, and to compare different administration times of detemir.Methods: This 20-week, multicenter, randomized, open-label, 3-arm, parallel-group trial was conducted at 91 centers across Europe and the United States. Men and women were eligible for participation if they were aged >= 18 years, had a body mass index (BMI) = 1 OAD. Patients were randomly assigned to receive an evening SC injection of detemir, a prebreakfast injection of detemir, or an evening injection of NPH insulin (1:1:1), administered at initial doses of 10 IU (U).Results: A total of 504 patients were enrolled (285 men, 219 women; mean [SD] age, 59 [11] years; mean [SD] BMI, 30 [5] kg/m(2); insulin detemir before breakfast, 168; insulin detemir evening, 170; NPH insulin evening, 166). The intent-to-treat population comprised 498 patients. Morning and evening detemir were associated with reductions in HbA(1c) similar to those with evening NPH (raw mean decreases, -1.58%, -1.48%, and -1.74%, respectively). Nine-point profile and fasting and predinner plasma glucose data found morning detemir to be associated with a different diurnal glycemic profile compared with the evening regimens. Compared with evening NPH, 24-hour and nocturnal hypoglycemia were reduced by 53% (P = 0.019) and 65% (P = 0.031), respectively, with evening detemir. Incidences of hypoglycemia did not differ significantly between groups that received morning and evening detemir, but nocturnal hypoglycemia was reduced further, by 87%, with morning detemir compared with evening NPH (P < 0.001). Weight gain was 1.2, 0.7, and 1.6 kg with morning detemir, evening detemir, and NPH, respectively (P = 0.005 for evening detemir vs NPH). No between-treatment differences were seen in other tolerability end points.Conclusions: The results of this study in patients whose type 2 DM was poorly controlled with >= 1 OAD suggest that insulin detemir QD in the morning or evening can be used to improve glycemic control. Compared with NPH, insulin detemir may offer some tolerability advantages in this role.