Efficacy and safety of visepegenatide as an add-on therapy to metformin in patients with type 2 diabetes: a randomised, double-blind, parallel, placebo-controlled, phase 3 study

Xiaoling Cai; Linong Ji; Mingxia Yuan; Jianhua Ma; Fang Bian; Sheli Li; Wuyan Pang; Shuang Yan; Huimin Zhou; Minghui Hou; Wenhui Li; Ying Jia; Li Liu; Ke Ding; Michael Xu

doi:10.1016/j.lanwpc.2024.101197

Efficacy and safety of visepegenatide as an add-on therapy to metformin in patients with type 2 diabetes: a randomised, double-blind, parallel, placebo-controlled, phase 3 study

Lancet Reg Health West Pac. 2024 Oct 3:51:101197. doi: 10.1016/j.lanwpc.2024.101197. eCollection 2024 Oct.

Authors

Xiaoling Cai¹, Linong Ji¹, Mingxia Yuan², Jianhua Ma³, Fang Bian⁴, Sheli Li⁵, Wuyan Pang⁶, Shuang Yan⁷, Huimin Zhou⁸, Minghui Hou⁹, Wenhui Li¹⁰, Ying Jia¹¹, Li Liu¹¹, Ke Ding¹¹, Michael Xu¹¹

Affiliations

¹ Peking University People's Hospital, Beijing, China.
² Beijing Friendship Hospital, Capital Medical University, Beijing, China.
³ Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
⁴ Cangzhou People's Hospital, Cangzhou, China.
⁵ Yanan University Affiliated Hospital, Yanan, China.
⁶ Huaihe Hospital of Henan University, Kaifeng, China.
⁷ The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
⁸ The First Hospital of Hebei Medical University, Shijiazhuang, China.
⁹ Affiliated Hospital of Hebei University, Hebei, China.
¹⁰ Peking Union Medical College, Beijing, China.
¹¹ PegBio Co., Ltd, Suzhou, China.

Abstract

Background: Visepegenatide, a once-weekly glucagon-like peptide-1 receptor agonist injection, demonstrated effective glycaemic control and good tolerability without the requirement of dose titration in the two completed phase 2 studies. We aimed to evaluate the efficacy and safety of visepegenatide in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin monotherapy in this phase 3 clinical study.

Methods: This multicentre phase 3 clinical study included a 24-week, randomised, placebo-controlled, double-blind period followed by a 28-week open-label extended treatment period. Patients (N = 620) aged ≥18 and ≤75 years with glycated haemoglobin (HbA_1c) ≥7.0% and ≤10.5% [≥53.0 and ≤91.27 mmol/mol], were randomized in a 1:1 ratio to receive visepegenatide 150-μg or placebo once-weekly subcutaneous injection during the double-blind period. Subsequently, the patients in the placebo group were switched to visepegenatide treatment (placebo→visepegenatide group), and the patients in the visepegenatide group continued the same treatment during the open-label extended treatment period. The primary endpoint was the change in HbA_1c from baseline to week 24.

Findings: At week 24, the placebo-adjusted least squares mean (LSM) change of HbA_1c was -0.57% (95% CI -0.71 to -0.43) with visepegenatide (p < 0.001). The proportion of patients achieving HbA_1c < 7.0% and ≤6.5% [<53 and ≤ 48 mmol/mol] was higher in the visepegenatide group versus the placebo group (115 [40.5%] vs 50 [17.9%]; p < 0.001, and 60 [21.1%] vs 17 [6.1%]; p < 0.001). Visepegenatide demonstrated a significant reduction in fasting plasma glucose and 2-h postprandial glucose compared with placebo. Trends in the improvement of these variables were maintained during the open-label extended treatment period. No severe gastrointestinal adverse event or severe hypoglycaemia was reported during the 52-week study period.

Interpretation: Once-weekly injection of visepegenatide 150 μg as an add-on treatment to metformin therapy significantly improved glycaemic control and was generally well tolerated in Chinese patients with T2DM who were inadequately controlled with metformin monotherapy.

Funding: The study was funded by PegBio Co., Ltd, Suzhou, China.

Keywords: Add-on therapy; GLP-1 receptor agonist; Metformin; Type 2 diabetes mellitus; Visepegenatide.