双时相门冬胰岛素50与人胰岛素50的疗效和安全性比较：一项随机交叉试验

Comparison of efficacy and safety between biphasic insulin aspart 50 and biphasic human insulin 50：A randomized crossover trial

目的观察对比中国2型糖尿病患者在联合二甲双胍基础上应用每日2次（ bid）双时相门冬胰岛素50（biphasic insulin aspart 50, BIAsp50）与双时相人胰岛素50（biphasic human insulin 50, BHI50）bid在标准餐试验时的血糖控制疗效。方法在中国14个中心进行了一项随机、开放、2阶段交叉设计试验。使用BHI50 bid和二甲双胍但血糖控制不佳的2型糖尿病患者经筛选合格后,被随机（1：1）分配至2个治疗序列（A：BIAsp50-BHI50,B：BHI50-BIAsp50）。在基线和为期4周的2个治疗阶段结束后,分别进行标准餐试验。研究的主要终点为标准餐试验时餐后2 h血糖（2h PPG）增幅,标准餐试验时的胰岛素剂量为每公斤体重0.3 IU。结果共计161例受试者被随机分入2个序列（序列A：81例,序列B：80例）并纳入分析。治疗4周后,标准餐试验后BIAsp50的2h PPG增幅均值低于BHI50,BIAsp50和BHI50间估计的治疗差异为-1.12 mmol/L（95%CI-1.66,-0.58, P＆lt;0.01）,表明BIAsp50优效于BHI50。 BIAsp50的0~2 h葡萄糖曲线下面积低于BHI50,BIAsp50和BHI50间估计的治疗差异为-38.8 mmol＆#183;L-1＆#183;min-1（95% CI-77.3,-0.26, P=0.049）；BIAsp50的2h PPG均值低于BHI50,BIAsp 50和BHI 50间估计的治疗差异为-0.58 mmol/L（95%CI-1.13,-0.03, P=0.040）。 BIAsp50的空腹血糖（FPG）均值高于BHI 50,BIAsp50和BHI50间估计的治疗差异为0.52 mmol/L（95%CI,0.18,0.86, P=0.003）。此外,BIAsp50的夜间低血糖发生率低于BHI50（1.13对2.86次/患者年,P＆lt;0.01）。结论在BHI50联合二甲双胍但血糖控制不佳的2型糖尿病患者中,在标准餐时BIAsp50较BHI50的餐后血糖控制更佳且耐受性更好。

Objective To investigate the efficacy of biphasic insulin aspart 50（BIAsp50）twice daily（bid） versusbiphasichumaninsulin50（BHI50）（bid）plusmetforminonbloodglucosecontrolfollowingastandardmealtest in Chinese patients with type 2 diabetes mellitus（T2DM）. Methods A randomized, open-label, 2-sequence, crossover trial for two 4-week treatment periods was conducted in 14 Chines institutes. Eligible subjects inadequately controlled with BHI50（bid）plus metformin were randomized to two sequences in a 1 ： 1 ratio（A：BIAsp50-BHI50, B：BHI50-BIAsp50 ） . Standard meal tests were performed at baseline and the ends of two periods within 4 weeks. Primary endpoint was 2h postprandial plasma glucose （ PPG） increment following standard meal test, with insulin dose standardized at 0. 3 IU/kg. Results A total of 161 subjects were randomized into two sequences（81 to sequence A, and 80 to sequence B） and finally analysed. After 4 weeks of treatment, mean 2h PPG increment with BIAsp50 was lower than that with BHI50 [ treatment difference of BIAsp50 vs BHI50： -1. 12 mmol/L （ 95% CI-1. 66,-0. 58）, P〈0. 01], suggesting superiority of BIAsp50 over BHI50. Incremental area under the curve for PPG（0-2 h）with BIAsp50 was lower than that with BHI50 [treatment difference：-38. 8 mmol＆#183;L-1＆#183;min-1（95%CI-77. 3,-0. 26）, P=0. 049], as was the mean 2h PPG [treatment difference：-0. 58 mmol/L（95% CI -1. 13,-0. 03）, P=0. 040]. The FPG value with BIAsp50 was higher than that with BHI50 [treatment difference：0. 52 mmol/L（95%CI 0. 18, 0. 86）, P=0. 003]. The rate of nocturnal hypoglycemia with BIAsp50 was lower than that with BHI50（1. 13 vs 2. 86 events per subject year, P〈0. 01）. Conclusion In patients with T2DM inadequately controlled with BHI50 plus metformin, BIAsp50 was proven to be well-tolerated with improved postprandial glucose control compared with BHI50.