Efficacy and safety of polyethylene glycol loxenatide monotherapy in type 2 diabetes patients: A multicentre, randomized, double-blind, placebo-controlled phase 3a clinical trial

摘要

Aim: To evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) monotherapy in type 2 diabetes (T2D) patients in China.Materials and Methods: In a multicentred, randomized, double-blinded, placebo-controlled phase 3a clinical trial, 361 patients with inadequate glycaemic 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 (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 < .0001). The proportions of patients with less than 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 because of AEs. Four (1.2%) patients (PEX168/100 μg: N = 3 [2.5%] and PEX168/200 μg: N = 1 [0.9%]) developed PEX168 antidrug antibodies.Conclusion: PEX168 monotherapy significantly improved glycaemic control in T2D patients with a safety profile resembling that of other glucagon-like peptide-1 receptor agonists.