Raz Itamar, Mouritzen Ulrik, Vaz Julius, Hershkovitz Tommy, Wainstein Julio, Harman-Boehm Ilana
Hadassah Ein Karem Medical Center, Jerusalem, Israel.
Clin Ther. 2003 Dec;25(12):3109-23. doi: 10.1016/s0149-2918(03)90095-6.
The incidence of type 2 diabetes mellitus (DM) is rapidly increasing worldwide. Results from large-scale studies show that tight blood glucose (BG) control improves the outcome of patients with type 2 DM.
This trial assessed the short-term efficacy and tolerability of adding a thiazolidinedione (rosiglitazone [ROS]) to existing sulfonylurea (SU) therapy (glibenclamide) compared with switching to combination treatment with a premixed insulin (biphasic insulin aspart 30 [BIAsp 30], a rapid-acting insulin analog) and the thiazolidinedione in a select group of patients with type 2 DM whose metabolic control was inadequate with SU monotherapy.
In this 6-week, multicenter, open-label, parallel-group trial, patients with type 2 DM whose BG level was not adequately controlled with glibenclamide monotherapy (glycosylated hemoglobin [HbA1c] 8%-13%) were randomized either to replace glibenclamide with BIAsp 30 (individually titrated dosages starting with 6-8 U BID) plus rosiglitazone (4 mg once daily) (BIAsp 30 + ROS group) or to add rosiglitazone (4 mg once daily) to their pretrial doses of glibenclamide (GLIB + ROS group). Patients measured their BG levels immediately before each of the 3 main meals, 90 minutes after the start of each meal, and at bedtime, and mean BG levels were calculated at weeks 0 (baseline), 1, 2, 4, 6, and at 2-week follow-up (week 8). The primary end point was change in mean daily BG level during treatment. Secondary end points included preprandial, postprandial, and bedtime BG levels, serum fructosamine level HbA, and fasting BG level, which were measured at each study visit. Tolerability was assessed using hematologic and biochemical parameters, vital signs, and physical examination.
Forty-nine patients (32 men, 17 women; mean [SD] age, 59.1 [8.9] years; mean [SD] body mass index, 27.7 [3.7] kg/m2) participated in the study. A significant difference was found between treatments in the change in mean daily BG level from baseline to week 6 (P=0.01). After the 6-week treatment period, change in mean serum fructosamine level was significantly greater for BIAsp 30 + ROS compared with GLIB + ROS (P=0.02). HbA1c decreased in both treatment groups from baseline to study end, but the difference between groups was nonsignificant. The changes in fasting BG from baseline to study end also were nonsignificant between groups. Both combinations were well tolerated.
This short-term study in patients with type 2 DM whose BG level was poorly controlled with glibenclamide monotherapy suggests that switching to a combination of BIAsp 30 + ROS was efficacious and well tolerated and provided an alternative to adding rosiglitazone to existing glibenclamide treatment. The study also suggests that BIAsp 30 may be associated with greater improvements in short-term metabolic control.
2型糖尿病（DM）在全球的发病率正在迅速上升。大规模研究结果表明，严格控制血糖（BG）可改善2型糖尿病患者的预后。
本试验评估了在一组单用磺脲类药物（SU）（格列本脲）治疗代谢控制不佳的2型糖尿病患者中，与换用预混胰岛素（门冬胰岛素30 [BIAsp 30]，一种速效胰岛素类似物）和噻唑烷二酮联合治疗相比，在现有SU治疗（格列本脲）基础上加用噻唑烷二酮（罗格列酮[ROS]）的短期疗效和耐受性。
在这项为期6周的多中心、开放标签、平行组试验中，单用格列本脲治疗血糖水平控制不佳（糖化血红蛋白[HbA1c] 8%-13%）的2型糖尿病患者被随机分为两组，一组用BIAsp 30（起始剂量6-8 U，每日两次，个体化滴定剂量）加罗格列酮（每日4 mg）替代格列本脲（BIAsp 30 + ROS组），另一组在其治疗前的格列本脲剂量基础上加用罗格列酮（每日4 mg）（GLIB + ROS组）。患者在每餐主餐前、每餐开始后90分钟以及睡前测量血糖水平，并在第0周（基线）、第1、2、4、6周以及2周随访（第8周）计算平均血糖水平。主要终点是治疗期间平均每日血糖水平的变化。次要终点包括餐前、餐后和睡前血糖水平、血清果糖胺水平、HbA1c以及空腹血糖水平，在每次研究访视时进行测量。使用血液学和生化参数、生命体征以及体格检查评估耐受性。
49例患者（32例男性，17例女性；平均[标准差]年龄，59.1 [8.9]岁；平均[标准差]体重指数，27.7 [3.7] kg/m2）参与了研究。从基线到第6周，治疗组间平均每日血糖水平变化存在显著差异（P = 0.01）。6周治疗期后，BIAsp 30 + ROS组平均血清果糖胺水平变化显著大于GLIB + ROS组（P = 0.02）。两个治疗组的HbA1c从基线到研究结束均有所下降，但组间差异无统计学意义。两组从基线到研究结束空腹血糖的变化也无统计学意义。两种联合治疗耐受性均良好。
这项针对单用格列本脲治疗血糖控制不佳的2型糖尿病患者的短期研究表明，换用BIAsp 30 + ROS联合治疗有效且耐受性良好，为在现有格列本脲治疗基础上加用罗格列酮提供了一种替代方案。该研究还表明，BIAsp 30可能与短期代谢控制的更大改善相关。
