Pharmacokinetics, safety, and tolerability of single- and multiple-dose exenatide once weekly in Chinese patients with type 2 diabetes mellitus

J Diabetes. 2013 Jun;5(2):127-35. doi: 10.1111/1753-0407.12020.

Abstract

Background: This open-label, single-period study assessed the pharmacokinetics, safety, tolerability, and pharmacodynamics of exenatide once weekly (q.w.), following single and multiple weekly subcutaneous (s.c.) injections in native Chinese patients with type 2 diabetes (T2D).

Methods: Patients (n = 25; mean [±SD] age 51.3 ± 8.2 years; body mass index 25.6 ± 2.4 kg/m(2) ; HbA1c 7.4 ± 1.2%; duration of diabetes 3.1 ± 3.1 years) previously treated with diet modification and exercise alone or incombination with stable metformin doses were enrolled in the study. Twenty-five patients received weekly doses of 2 mg, s.c., exenatide q.w. for 10 weeks, followed by 10 weeks observation. Pharmacokinetic parameters of exenatide, fasting plasma glucose (FPG), HbA1c, and body weight were summarized using descriptive statistics.

Results: Steady state plasma exenatide concentrations (299 pg/mL) were attained within 8 weeks. Exenatide q.w. was generally well tolerated, and the majority of adverse events reported were mild in severity. The most frequent study drug-related adverse events were diarrhea and vomiting. Decreases were observed from baseline to 10 weeks in FPG (~3.0 mmol/L), HbA1c (~1.0%), and body weight (~3.8 kg).

Conclusions: This is the first clinical trial of exenatide q.w. in native Chinese patients with T2D. The results suggest that exenatide q.w. has a pharmacokinetic profile in this patient population similar to that observed in other ethnic and racial populations, and appears to be safe and generally well tolerated, with the potential to improve glycemic control and decrease body weight without increasing the risk of hypoglycemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People
  • Blood Glucose / metabolism
  • Body Mass Index
  • Body Weight
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drug Tolerance
  • Exenatide
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / therapeutic use
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Peptides / pharmacokinetics*
  • Peptides / therapeutic use
  • Venoms / pharmacokinetics*
  • Venoms / therapeutic use

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • hemoglobin A1c protein, human
  • Exenatide