The pharmacokinetics, pharmacodynamics, and tolerability of liraglutide, a once-daily human GLP-1 analogue, after multiple subcutaneous administration in healthy Chinese male subjects

J Clin Pharmacol. 2011 Dec;51(12):1620-7. doi: 10.1177/0091270010389468. Epub 2011 Jan 27.

Abstract

In this single-center, randomized, double-blind, within dose group, placebo-controlled, dose escalation trial, the pharmacokinetics, pharmacodynamics, tolerability, and safety of liraglutide were evaluated in 37 healthy Chinese subjects. Subjects were randomized to 1 of 3 dose groups (0.6, 1.2, or 1.8 mg), and within each group, randomized to liraglutide or placebo (3:1). All subjects started at 0.6 mg liraglutide (or placebo) once daily for 1 week, and the dose was increased for dose groups 1.2 mg and 1.8 mg in weekly steps of 0.6 mg to the predefined dose targets. Liraglutide or placebo was administered once daily by subcutaneous injection for 21 consecutive days. The dose relationships of AUC(0-24h), C(max), and C(trough) at steady state do not deviate in a relevant way from dose proportionality. t(max) and t(1/2) were 8 hours (median) and 11.2 to 12.2 hours (geometric mean), respectively. The plasma glucose levels in all liraglutide groups were decreased, while reduced serum insulin level was observed in the 1.2- and 1.8-mg groups after liraglutide treatment. The most common adverse events were of gastrointestinal origin. Other adverse events were comparable between the liraglutide and placebo groups. Liraglutide was well tolerated in healthy Chinese subjects. No major safety concerns were identified.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Pain / chemically induced
  • Adolescent
  • Adult
  • Area Under Curve
  • Asian People
  • Blood Glucose / analysis
  • Diarrhea / chemically induced
  • Double-Blind Method
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / pharmacokinetics
  • Glucagon-Like Peptide 1 / pharmacology
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology*
  • Injections, Subcutaneous
  • Insulin / blood
  • Liraglutide
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Young Adult

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Liraglutide
  • Glucagon-Like Peptide 1