PMID- 32206903 OWN - NLM STAT- MEDLINE DCOM- 20200923 LR - 20221207 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 57 IP - 8 DP - 2020 Aug TI - Efficacy and safety of generic exenatide injection in Chinese patients with type 2 diabetes: a multicenter, randomized, controlled, non-inferiority trial. PG - 991-1000 LID - 10.1007/s00592-020-01510-y [doi] AB - AIMS: This study aimed to compare the efficacy and safety of generic exenatide with branded exenatide Byetta((R)) 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 - 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. FAU - Yang, Jin AU - Yang J AUID- ORCID: 0000-0001-6004-955X AD - Department of Endocrinology and Metabolism, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, People's Republic of China. FAU - Xiao, Wenhua AU - Xiao W AD - Department of Endocrinology and Metabolism, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, People's Republic of China. FAU - Guo, Lixin AU - Guo L AD - Department of Endocrinology, Beijing Hospital, Beijing, 100730, People's Republic of China. FAU - Li, Quanmin AU - Li Q AD - Department of Endocrinology, PLA Rocket Force Characteristic Medical Center, Beijing, 100088, People's Republic of China. FAU - Zhong, Liyong AU - Zhong L AD - Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People's Republic of China. FAU - Yang, Jinkui AU - Yang J AD - Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China. FAU - Yang, Jing AU - Yang J AD - Department of Endocrinology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, People's Republic of China. FAU - Gao, Yongyi AU - Gao Y AD - Department of Endocrinology, People's Hospital of Hainan Province, Haikou, 570311, People's Republic of China. FAU - Tian, Qing AU - Tian Q AD - Department of Endocrinology and Metabolism, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, People's Republic of China. FAU - Hong, Tianpei AU - Hong T AUID- ORCID: 0000-0002-5744-5129 AD - 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. LA - eng GR - 2018YFC1313900/National Basic Research Program of China (973 Program)/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20200323 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Blood Glucose) RN - 0 (Drugs, Generic) RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Secretagogues) RN - 9100L32L2N (Metformin) RN - 9P1872D4OL (Exenatide) SB - IM MH - Adult MH - Blood Glucose/drug effects/metabolism MH - China MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Therapy, Combination MH - Drugs, Generic/administration & dosage/adverse effects MH - Equivalence Trials as Topic MH - Exenatide/*administration & dosage/*adverse effects MH - Female MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/administration & dosage/adverse effects MH - Injections MH - Insulin/metabolism MH - Male MH - Metformin/administration & dosage/adverse effects MH - Middle Aged MH - Secretagogues/administration & dosage/adverse effects MH - Treatment Outcome OTO - NOTNLM OT - Exenatide OT - Generic medicine OT - Non-inferiority trial OT - Type 2 diabetes mellitus EDAT- 2020/03/25 06:00 MHDA- 2020/09/24 06:00 CRDT- 2020/03/25 06:00 PHST- 2020/02/01 00:00 [received] PHST- 2020/02/26 00:00 [accepted] PHST- 2020/03/25 06:00 [pubmed] PHST- 2020/09/24 06:00 [medline] PHST- 2020/03/25 06:00 [entrez] AID - 10.1007/s00592-020-01510-y [pii] AID - 10.1007/s00592-020-01510-y [doi] PST - ppublish SO - Acta Diabetol. 2020 Aug;57(8):991-1000. doi: 10.1007/s00592-020-01510-y. Epub 2020 Mar 23.