title: Pharmacokinetics and pharmacodynamics of a polyethylene glycol (PEG)-conjugated GLP-receptor agonist once weekly in Chinese patients with type 2 diabetes.
abstract: This multi-center, randomized, double-blind, multiple dose-escalation study was conducted to assess the pharmacokinetics and pharmacodynamics of a newly developed polyethylene glycol (PEG)-conjugated glucagon-like peptide-1 (GLP-1) receptor agonist, PEX168 once weekly in Chinese patients with type 2 diabetes (T2DM). Fifty patients aged 20-65 years, either treatment-naive or having been treated with single oral antidiabetic agents were eligible. Antidiabetic agents were stopped for 14 days before the study was initiated. Patients were allocated randomly into groups with subcutaneous PEX168 or placebo once-weekly for 8 weeks followed by 6 weeks observation. From baseline to 8 weeks, HbA1c were decreased by up to 0.0, 0.2, 0.6, 0.9, and -0.4% in the 50, 100, 200, 300 μg PEX168 groups, and placebo group respectively. The mean elimination half-life of PEX168 was 131.8-139.8 hours. The mean tmax was 67.3 hours. Steady-state plasma PEX168 concentrations were attained after 4 weeks. PEX168 once-weekly were tolerable by the patients: adverse effects reported ranged from 'mild' to 'moderate'. The most frequent drug-related adverse effects were nausea, vomiting, and diarrhea of mild to moderate severity. Administration of the PEG-conjugated GLP-1 receptor agonist PEX168 resulted in dose-proportional pharmacokinetic and antidiabetic pharmacodynamic activity.
authors.affiliation: Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
authors.forename: Guang-Ran
authors.initials: GR
authors.lastname: Yang
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Zhao
authors.forename: Fan
authors.initials: F
authors.lastname: Jin
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Shi
authors.forename: Jin-Kui
authors.initials: JK
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019518:Postprandial Period; D018027:Receptors, Glucagon / Q000819:agonists*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D010455:Peptides; D011092:Polyethylene Glycols; D018027:Receptors, Glucagon; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human; C000601947:polyethylene glycol loxenatide
keywords: diabetes; glucagon-like peptide-1; pharmacodynamics; pharmacokinetics; safety