Yki-Järvinen H, Kauppinen-Mäkelin R, Tiikkainen M, Vähätalo M, Virtamo H, Nikkilä K, Tulokas T, Hulme S, Hardy K, McNulty S, Hänninen J, Levänen H, Lahdenperä S, Lehtonen R, Ryysy L
Department of Medicine, University of Helsinki, P.O. Box 340, FIN-00029 HUCH, Helsinki, Finland.
Diabetologia. 2006 Mar;49(3):442-51. doi: 10.1007/s00125-005-0132-0. Epub 2006 Feb 3.
AIMS/HYPOTHESIS: In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia.
In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups.
During the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/-0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l for patients reaching vs those not reaching target, p<0.01).
CONCLUSIONS/INTERPRETATION: Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinner time hyperglycaemia compared with NPH+MET.
目的/假设：在2型糖尿病患者中，我们比较了甘精胰岛素与二甲双胍联合治疗9个月和低精蛋白胰岛素与二甲双胍联合治疗9个月的效果。主要关注糖化血红蛋白（HbA₁c）的变化；次要关注日间血糖谱和症状性低血糖。
在这项由研究者发起的开放、平行组临床试验中，涉及7个中心，110例口服降糖药（90%使用磺脲类加二甲双胍）治疗但血糖控制不佳（HbA₁c≥8.0%）且未使用过胰岛素的2型糖尿病患者被随机分为接受甘精胰岛素联合二甲双胍（G+MET）或低精蛋白胰岛素联合二甲双胍（NPH+MET）治疗36周。患者学习如何自我调整胰岛素剂量，并使用调制解调器将家庭血糖监测结果发送至治疗中心。目标是使两组的空腹血糖（FPG）均达到4.0至5.5 mmol/L。
在最后12周期间，G+MET组和NPH+MET组的FPG平均分别为5.75±0.02和5.96±0.03 mmol/L（p<0.001），胰岛素剂量分别为68±5和70±6 IU/天（0.69±0.05和0.66±0.04 IU·kg⁻¹·天⁻¹，无显著差异）。在36周时，平均HbA₁c分别为7.14±0.12%和7.16±0.14%（无显著差异）。在最初12周内，G+MET组的症状性低血糖（但未确诊）显著低于NPH+MET组（4.1±0.8次/患者年比9.0±2.3次/患者年，p<0.05），但此后无显著差异。在整个36周的研究中，NPH+MET组晚餐前血糖水平（10.1±0.3 mmol/L）高于G+MET组（8.6±0.3 mmol/L，p=0.002）。关于基线特征，如初始血糖或C肽，血糖控制良好（HbA₁c<7.0%）的患者与未达到良好控制的患者之间无差异。在以下方面存在差异：研究中心之间、导入期和胰岛素治疗期间的体重增加以及最后12周的FPG（达到目标的患者与未达到目标的患者分别为5.7±0.2 vs 6.7±0.3 mmol/L，p<0.01）。
结论/解读：G+MET和NPH+MET均可实现良好的血糖控制。与NPH+MET相比，使用G+MET可在最初12周减少症状性低血糖和晚餐时高血糖。
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