Jin Yang1, Wenhua Xiao1, Lixin Guo2, Quanmin Li3, Liyong Zhong4, Jinkui Yang5, Jing Yang6, Yongyi Gao7, Qing Tian1, Tianpei Hong8. 1. Department of Endocrinology and Metabolism, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, People's Republic of China. 2. Department of Endocrinology, Beijing Hospital, Beijing, 100730, People's Republic of China. 3. Department of Endocrinology, PLA Rocket Force Characteristic Medical Center, Beijing, 100088, People's Republic of China. 4. Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People's Republic of China. 5. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China. 6. Department of Endocrinology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, People's Republic of China. 7. Department of Endocrinology, People's Hospital of Hainan Province, Haikou, 570311, People's Republic of China. 8. Department of Endocrinology and Metabolism, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, People's Republic of China. tpho66@bjmu.edu.cn.
Abstract
AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
RCT Entities:
AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Entities:
Keywords:
Exenatide; Generic medicine; Non-inferiority trial; Type 2 diabetes mellitus
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