Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study.

Abstract

AIMS/HYPOTHESIS:

Glucagon-like peptide 1 receptor agonists (GLP-1 RA) such as exenatide are used as monotherapy and add-on therapy for maintaining glycaemic control in patients with type 2 diabetes mellitus. The current study investigated the safety and efficacy of once-weekly PB-119, a PEGylated exenatide injection, in treatment-naive patients with type 2 diabetes.

METHODS:

In this Phase II, randomised, placebo-controlled, double-blind study, we randomly assigned treatment-naive Chinese patients with type 2 diabetes in a 1:1:1:1 ratio to receive subcutaneous placebo or one of three subcutaneous doses of PB-119 (75, 150, and 200 μg) for 12 weeks. The primary endpoint was the change in HbA1c from baseline to week 12, and other endpoints were fasting plasma glucose, 2 h postprandial glucose (PPG), and proportion of patients with HbA1c < 53 mmol/mol (<7.0%) and ≤48 mmol/mol (≤6.5%) at 2, 4, 8 and 12 weeks of treatment. Safety was assessed in all patients who received at least one dose of study drug.

RESULTS:

We randomly assigned 251 patients to one of the four treatment groups (n = 62 in placebo and 63 each in PB-119 75 μg, 150 μg and 200 μg groups). At the end of 12 weeks, mean differences in HbA1c in the treatment groups were -7.76 mmol/mol (95% CI -9.23, -4.63, p < 0.001) (-0.72%, 95% CI -1.01, -0.43), -12.89 mmol/mol (95% CI -16.05, -9.72, p < 0.001) (-1.18%, 95% CI -1.47, -0.89) and -11.14 mmol/mol (95% CI -14.19, -7.97, p <0 .001) (-1.02%, 95% CI -1.30, -0.73) in the 75 μg, 150 μg and 200 μg PB-119 groups, respectively, compared with that in the placebo group after adjusting for baseline HbA1c. Similar results were also observed for other efficacy endpoints across different time points. There was no incidence of treatment-emergent serious adverse event, severe hypoglycaemia or death.

CONCLUSIONS/INTERPRETATION:

All tested PB-119 doses had superior efficacy compared with placebo and were safe and well tolerated over 12 weeks in treatment-naive Chinese patients with type 2 diabetes.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT03520972 FUNDING: The study was funded by National Major Scientific and Technological Special Project for Significant New Drugs Development and PegBio.

• Authors: Linong Ji, Ying Du, Min Xu, Xiangjun Zhou, Zhaohui Mo, Jianhua Ma, Jiarui Li, Yufeng Li, Jingna Lin, Yanjun Wang, Jing Yang, Weihong Song, Hui Jin, Shuguang Pang, Hui Liu, Ping Li, Jie Liu, Minxiu Yao, Wenhui Li, Xiaohong Jiang, Feixia Shen, Houfa Geng, Haifeng Zhou, Jianmin Ran, Minxiang Lei, Yinghong Du, Shandong Ye, Qingbo Guan, Wenshan Lv, Huiwen Tan, Tao Chen, Jinkui Yang, Guijun Qin, Shiyun Li, Lei Chen
• Journal: Diabetologia (Diabetologia) Vol. 64 Issue 5 Pg. 1066-1078 (05 2021) ISSN: 1432-0428 [Electronic] Germany
• PMID: 33687487 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Glycated Hemoglobin A
• Polyethylene Glycols
• Exenatide

Topics

• Adolescent
• Adult
• Aged
• Blood Glucose (drug effects, metabolism)
• China (epidemiology)
• Diabetes Mellitus, Type 2 (blood, drug therapy, epidemiology)
• Double-Blind Method
• Exenatide (chemistry, therapeutic use)
• Female
• Glycated Hemoglobin (drug effects, metabolism)
• Humans
• Male
• Middle Aged
• Polyethylene Glycols (chemistry)
• Treatment Outcome
• Young Adult