Objective: To compare the efficacy and safety of Tonghua Dongbao's insulin aspart injection (Rishulin) and NovoRapid (Novo Nordisk) in the treatment of diabetes. Methods: A 26-week, randomized, open-label, parallel-group, positive control drug and non-inferiority trial was conducted in 23 centers in China. A total of 563 diabetes with poor blood glucose control treated with insulin for at least 3 months before were included. The subjects were randomized(stratified block random method) into those receiving Rishulin or NovoRapid at a ratio of 3∶1. Both groups were combined with basal insulin (Lantus). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to the end of 24 weeks of treatment. Results: For full analysis set, after 24 weeks of treatment, HbA1c level of Ruishulin group decreased from (8.66±1.28)% to (7.77±1.09)% (P<0.001), and that of NovoRapid group decreased from (8.47±1.28) % to (7.65±0.97) % (P<0.001). Treatment difference in HbA1c (NovoRapid group-Ruishulin group) was -0.061% (95%CI -0.320-0.199). HbA1c<7.0% target reacing rates were 24.26% and 21.21% (P=0.456), and HbA1c<6.5% target reacing rates were 9.65% and 6.82% (P=0.310) in Ruishulin group and NovoRapid group, repectively. The standard 2 hours postprandial blood glucose (2hPG) in Ruishulin group decreased from (16.23±5.22) mmol/L to (12.65±4.57) mmol/L (P<0.001), and 2hPG in NovoRapid group decreased from (16.13±5.37) mmol/L to (11.91)±4.21) mmol/L (P<0.001). The fingertips blood glucose at 7-point of both groups exhibited varying degrees of reduction compared with those at baseline, repectively. Positive ratios of specific antibodies were 31.68% in Ruishulin group and 36.36% in NovoRapid group (P=0.320). Ratios of negative to positive were 7.43% and 10.61% (P=0.360), and ratios of positive to negative were 10.40% and 7.58% (P=0.360) in Ruishulin group and NovoRapid group, respectively. The incidence of hypoglycemia was 60.05% and 55.40% (P=0.371), and the incidence of adverse events was 76.60% and 77.70% (P=0.818) in Ruishulin group and NovoRapid group, respectively. Conclusions: Rishulin is not inferior to NovoRapid, and has shown good efficacy and safety. It can be an ideal choice for clinicians in patients with poor blood glucose control with insulin.
目的： 比较两种门冬胰岛素注射液锐舒霖与诺和锐治疗糖尿病的有效性与安全性。 方法： 本研究为多中心、为期26周、随机、开放、平行分组、阳性对照药物与非劣效临床试验，共纳入563例使用胰岛素至少3个月血糖控制不佳的糖尿病患者，受试者根据分层区组随机方法以3∶1的比例随机接受锐舒霖或诺和锐治疗，均联合应用基础胰岛素（来得时）。主要终点指标为治疗24周后糖化血红蛋白（HbA1c）相对基线的变化。 结果： 治疗24周后全分析集（FAS），锐舒霖组的HbA1c从基线（8.66±1.28）%下降到（7.77±1.09）%（P<0.001），诺和锐组（8.47±1.28）%下降到（7.65±0.97）%（P<0.001），两组差异（诺和锐组-锐舒霖组）为-0.061%（95%CI-0.320~0.199）。锐舒霖组和诺和锐组 HbA1c<7.0%达标率为24.26%和21.21%（P=0.456），HbA1c<6.5%达标率为9.65%和6.82%（P=0.310）；锐舒霖组标准餐后2h血糖（2hPG）从（16.23±5.22）mmol/L下降到（12.65±4.57）mmol/L（P<0.001），诺和锐组从（16.13±5.37）mmol/L下降到（11.91±4.21）mmol/L（P<0.001）；两组7点指尖血糖均较基线有不同程度下降。两组特异性抗体的阳性比例为31.68%和36.36%（P=0.320），阴性转阳性比例为7.43%和10.61%（P=0.360），阳性转阴性比例为10.40%和7.58%（P=0.360）。两组低血糖事件发生率为60.05%比55.40%（P=0.371）；两组不良事件发生率为76.60%比77.70%（P=0.818）。 结论： 锐舒霖非劣效于诺和锐，具有良好的有效性与安全性，可作为临床医师使用胰岛素血糖控制不佳患者的理想选择。.