Yki-Järvinen H, Ryysy L, Nikkilä K, Tulokas T, Vanamo R, Heikkilä M
University of Helsinki, Finland.
Ann Intern Med. 1999 Mar 2;130(5):389-96. doi: 10.7326/0003-4819-130-5-199903020-00002.
Compared with other insulin regimens, combination therapy with oral hypoglycemic agents and bedtime insulin produces similar improvement in glycemic control but induces less weight gain.
To determine whether bedtime insulin regimens differ with respect to their effects on weight gain in patients with type 2 diabetes.
Randomized, controlled trial.
Four outpatient clinics at central hospitals.
96 patients (mean age, 58 +/- 1 years; mean body mass index, 29 +/- 1 kg/m2) whose type 2 diabetes was poorly controlled with sulfonylurea therapy (mean glycosylated hemoglobin value, 9.9% +/- 0.2%; mean fasting plasma glucose level, 11.9 +/- 0.3 mmol/L [214 +/- 5 mg/dL]).
Random assignment to 1 year of treatment with bedtime intermediate-acting insulin plus glyburide (10.5 mg) and placebo, metformin (2 g) and placebo, glyburide and metformin, or a second injection of intermediate-acting insulin in the morning. Patients were taught to adjust the bedtime insulin dose on the basis of fasting glucose measurements.
Body weight, biochemical and symptomatic hypoglycemias, and indices of glycemic control.
At 1 year, body weight remained unchanged in patients receiving bedtime insulin plus metformin (mean change, 0.9 +/- 1.2 kg; P < 0.001 compared with all other groups) but increased by 3.9 +/- 0.7 kg, 3.6 +/- 1.2 kg, and 4.6 +/- 1.0 kg in patients receiving bedtime insulin plus glyburide, those receiving bedtime insulin plus both oral drugs, and those receiving bedtime and morning insulin, respectively. The greatest decrease in the glycosylated hemoglobin value was observed in the bedtime insulin and metformin group (from 9.7% +/- 0.4% to 7.2% +/- 0.2% [difference, -2.5 +/- 0.4 percentage points] at 1 year; P < 0.001 compared with 0 months and P < 0.05 compared with other groups). This group also had significantly fewer symptomatic and biochemical cases of hypoglycemia (P < 0.05) than the other groups.
Combination therapy with bedtime insulin plus metformin prevents weight gain. This regimen also seems superior to other bedtime insulin regimens with respect to improvement in glycemic control and frequency of hypoglycemia.
与其他胰岛素治疗方案相比，口服降糖药与睡前胰岛素联合治疗在血糖控制方面改善相似，但体重增加较少。
确定不同的睡前胰岛素治疗方案对2型糖尿病患者体重增加的影响是否存在差异。
随机对照试验。
中心医院的四家门诊诊所。
96例患者（平均年龄58±1岁；平均体重指数29±1kg/m²），其2型糖尿病采用磺脲类药物治疗效果不佳（平均糖化血红蛋白值9.9%±0.2%；平均空腹血糖水平11.9±0.3mmol/L[214±5mg/dL]）。
随机分配接受为期1年的治疗，分别为睡前中效胰岛素加格列本脲（10.5mg）和安慰剂、二甲双胍（2g）和安慰剂、格列本脲和二甲双胍，或早晨追加一次中效胰岛素注射。指导患者根据空腹血糖测量结果调整睡前胰岛素剂量。
体重、生化性及症状性低血糖以及血糖控制指标。
1年后，接受睡前胰岛素加二甲双胍治疗的患者体重保持不变（平均变化0.9±1.2kg；与所有其他组相比，P<0.001），而接受睡前胰岛素加格列本脲治疗的患者、接受睡前胰岛素加两种口服药物治疗的患者以及接受睡前和早晨胰岛素治疗的患者体重分别增加了3.9±0.7kg、3.6±1.2kg和4.6±1.0kg。睡前胰岛素和二甲双胍组糖化血红蛋白值下降幅度最大（1年后从9.7%±0.4%降至7.2%±0.2%[差值为-2.5±0.4个百分点]；与0个月时相比，P<0.001，与其他组相比，P<0.05）。该组的症状性及生化性低血糖病例也明显少于其他组（P<0.05）。
睡前胰岛素加二甲双胍联合治疗可防止体重增加。在血糖控制改善及低血糖发生频率方面，该方案似乎也优于其他睡前胰岛素治疗方案。
