Department of Endocrinology and Metabolism, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, People's Republic of China.
Department of Endocrinology, Beijing Hospital, Beijing, 100730, People's Republic of China.
Acta Diabetol. 2020 Aug;57(8):991-1000. doi: 10.1007/s00592-020-01510-y. Epub 2020 Mar 23.
This study aimed to compare the efficacy and safety of generic exenatide with branded exenatide Byetta in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues.
A multicenter, randomized, controlled, non-inferiority trial was performed. A total of 240 patients with T2DM and glycated hemoglobin (HbA1c) ≥ 7% (53 mmol/mol) to ≤ 9.0% (75 mmol/mol) on monotherapy or combination therapy of metformin and insulin secretagogues for at least 3 months were randomized into generic exenatide or branded exenatide groups with a 1:1 ratio for 16 weeks of treatment. The primary endpoint was the change in HbA1c levels from baseline at week 16, with a non-inferiority margin of - 0.35% (- 3.83 mmol/mol) (lower bound of one-sided 95% confidence interval (CI) > - 0.35% (- 3.83 mmol/mol)). Secondary endpoints included the proportion of participants achieving HbA1c < 7% (53 mmol/mol), the changes in fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG) following a standard meal, 7-point self-monitoring blood glucose (SMBG) profiles, body weight change from baseline at week 16 and the change in HbA1c levels from baseline at week 8. Safety issues were also evaluated.
After 16 weeks of treatment, HbA1c levels decreased significantly from baseline in the two groups, with a reduction of - 1.10% ± 1.31% (- 12.0 mmol/mol ± 14.3 mmol/mol) in the generic exenatide group and - 1.08% ± 1.11% (- 11.8 mmol/mol ± 12.1 mmol/mol) in the branded exenatide group (both P < 0.001). The least-squares mean difference of HbA1c reduction between the two groups was - 0.03% (- 0.33 mmol/mol), with a lower one-sided 95% CI limit of - 0.27% (- 2.95 mmol/mol), which was higher than the prespecified non-inferiority margin of - 0.35% (- 3.83 mmol/mol). Moreover, there were no significant differences in the proportion of participants achieving HbA1c < 7% (53 mmol/mol) and the changes in FPG, 2hPG, 7-point SMBG profiles and body weight at week 16 and the change in HbA1c levels from baseline at week 8 (all P > 0.05) between the two groups. The incidence of adverse events, including the incidence of hypoglycemia (18.3% and 17.5%, respectively), was similar for the generic and branded exenatide groups (P > 0.05).
In patients with T2DM inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues, add-on treatment with generic exenatide demonstrated non-inferiority to branded exenatide in terms of improvements in HbA1c after 16 weeks of treatment. Furthermore, the two drugs were also similar for other efficacy endpoints and safety profile. Trial registration Chinese Clinical Trial Registry: ChiCTR-IPR-15006558, Date registered May 27, 2015.
本研究旨在比较国产艾塞那肽与品牌艾塞那肽（百泌达）在二甲双胍和胰岛素促分泌剂联合治疗血糖控制不佳的 2 型糖尿病（T2DM）患者中的疗效和安全性。
这是一项多中心、随机、对照、非劣效性临床试验。共纳入 240 例 T2DM 患者，这些患者在接受二甲双胍和胰岛素促分泌剂联合治疗至少 3 个月后，糖化血红蛋白（HbA1c）≥7%（53mmol/mol）但≤9.0%（75mmol/mol），按 1:1 的比例随机分为国产艾塞那肽或品牌艾塞那肽组，治疗 16 周。主要终点为治疗 16 周时 HbA1c 水平与基线相比的变化，非劣效性边界为-0.35%（-3.83mmol/mol）（下限单侧 95%置信区间（CI）> -0.35%（-3.83mmol/mol））。次要终点包括达到 HbA1c<7%（53mmol/mol）的参与者比例、空腹血糖（FPG）、标准餐餐后 2 小时血糖（2hPG）、7 点自我监测血糖（SMBG）谱、治疗 16 周时体重与基线相比的变化以及治疗 8 周时 HbA1c 水平与基线相比的变化。还评估了安全性问题。
治疗 16 周后，两组患者的 HbA1c 水平均较基线显著下降，国产艾塞那肽组下降 1.10%±1.31%（-12.0mmol/mol±14.3mmol/mol），品牌艾塞那肽组下降 1.08%±1.11%（-11.8mmol/mol±12.1mmol/mol）（均 P<0.001）。两组间 HbA1c 降低的最小二乘均数差值为-0.03%（-0.33mmol/mol），下限单侧 95%CI 限为-0.27%（-2.95mmol/mol），高于预设的非劣效性边界-0.35%（-3.83mmol/mol）。此外，两组患者治疗 16 周时达到 HbA1c<7%（53mmol/mol）的比例、FPG、2hPG、7 点 SMBG 谱和体重的变化以及治疗 8 周时 HbA1c 水平与基线相比的变化均无显著差异（均 P>0.05）。两组患者低血糖（分别为 18.3%和 17.5%）的不良反应发生率相似（P>0.05）。
在二甲双胍和胰岛素促分泌剂联合治疗血糖控制不佳的 T2DM 患者中，加用国产艾塞那肽治疗 16 周后，在改善 HbA1c 方面与品牌艾塞那肽相比非劣效。此外，两种药物在其他疗效终点和安全性方面也相似。试验注册中国临床试验注册中心：ChiCTR-IPR-15006558，注册日期 2015 年 5 月 27 日。
