Efficacy and safety of polyethylene glycol loxenatide (PEX168) monotherapy in type 2 diabetes patients: a multicenter, randomized, double-blind, placebo-controlled, phase 3a clinical trial.

AIM To evaluate the efficacy and safety of PEX168 monotherapy in type 2 diabetes (T2DM) patients in China. MATERIALS AND METHODS In a multicentered, randomized, double-blinded placebo-controlled phase 3a clinical trial, 361 patients with inadequate glycemic control (HbA1c, 7.0-10.5%; fasting plasma glucose, <13.9 mmol/L) were randomized (1:1:1) for weekly subcutaneous injections: placebo, PEX168/100 μg, or PEX168/200 μg. The 24-week treatment was followed by a 28-week extension, during which placebo-treated patients were randomly assigned to PEX168/100 μg or PEX168/200 μg. The primary efficacy endpoint was the HbA1c change from baseline to week 24. RESULTS The three groups had similar demographics and baseline characteristics. The HbA1c least-square mean [LSM (95% CI)] change from baseline to week 24 was greater for PEX168/100 μg [-1.02% (-1.21, -0.83)] and PEX168/200 μg [-1.34% (-1.54, -1.15)] than for placebo [-0.17% (-0.36, 0.02)]; (superiority: p < 0.0001). The proportions of patients with <7% HbA1c in the placebo, PEX168/100 μg, and PEX168/200 μg groups were 15.7%, 34.7%, and 46.6%, respectively. Common gastrointestinal adverse events (AEs) were nausea (5.6%, 10.0%, and 0% for PEX168/100 μg, PEX168/200 μg, and placebo, respectively) and vomiting (2.4%, 8.3%, and 0% for PEX168/100 μg, PEX168/200 μg, and placebo, respectively). Six (1.6%) patients [PEX168/100 μg: N = 2 (1.6%), PEX168/200 μg: N = 3 (2.5%), and placebo: N = 1 (0.8%)] discontinued treatment due to AEs. Four (1.2%) patients [PEX168/100 μg: N = 3 (2.5%), and PEX168/200 μg: N = 1 (0.9%)] developed PEX168 anti-drug antibodies. CONCLUSION PEX168 monotherapy significantly improved glycemic control in T2DM patients with a safety profile resembling that of other GLP-1 receptor agonists. This article is protected by copyright. All rights reserved.