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

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.