Efficacy and safety of generic exenatide injection in Chinese patients with type 2 diabetes: a multicenter, randomized, controlled, non-inferiority trial.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9200299 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-5233 (Electronic) Linking ISSN: 09405429 NLM ISO Abbreviation: Acta Diabetol Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin : Springer International, c1991-

Diabetes Mellitus, Type 2/*drug therapy ; Exenatide/*administration & dosage ; Exenatide/*adverse effects; Adult ; Blood Glucose/drug effects ; Blood Glucose/metabolism ; China ; Diabetes Mellitus, Type 2/blood ; Drug Therapy, Combination ; Drugs, Generic/administration & dosage ; Drugs, Generic/adverse effects ; Equivalence Trials as Topic ; Female ; Glycated Hemoglobin/analysis ; Humans ; Hypoglycemia/chemically induced ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/adverse effects ; Injections ; Insulin/metabolism ; Male ; Metformin/administration & dosage ; Metformin/adverse effects ; Middle Aged ; Secretagogues/administration & dosage ; Secretagogues/adverse effects ; Treatment Outcome

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.

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2018YFC1313900 National Basic Research Program of China (973 Program)

Keywords: Exenatide; Generic medicine; Non-inferiority trial; Type 2 diabetes mellitus

0 (Blood Glucose)
0 (Drugs, Generic)
0 (Glycated Hemoglobin A)
0 (Hypoglycemic Agents)
0 (Insulin)
0 (Secretagogues)
9100L32L2N (Metformin)
9P1872D4OL (Exenatide)

Date Created: 20200325 Date Completed: 20200923 Latest Revision: 20221207

20240628

10.1007/s00592-020-01510-y

32206903