Absence of QTc prolongation in a thorough QT study with subcutaneous liraglutide, a once-daily human GLP-1 analog for treatment of type 2 diabetes

J Clin Pharmacol. 2009 Nov;49(11):1353-62. doi: 10.1177/0091270009339189. Epub 2009 Sep 8.

Abstract

The objective of this study was to establish effects of liraglutide on the QTc interval. In this randomized, placebo-controlled, double-blind crossover study, 51 healthy participants were administered placebo, 0.6, 1.2, and 1.8 mg liraglutide once daily for 7 days each. Electrocardiograms were recorded periodically over 24 hours at the end of placebo and highest dosing periods. Four different models for QT correction were used: QTci, as the primary endpoint, and QTciL, QTcF, and QTcB as secondary endpoints. The upper bound of the 1-sided 95% confidence interval for time-matched, baseline-corrected, placebo-subtracted QTc intervals was <10 ms for all 4 correction methods. Moxifloxacin (400 mg) increased QTc intervals by 10.6 to 12.3 ms at 2 hours. There was no concentration-exposure dependency on QTc interval changes by liraglutide and no QTc thresholds above 500 ms or QTc increases >60 ms. The authors conclude that liraglutide caused no clinically relevant increases in the QTc interval.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aza Compounds / adverse effects
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Electrocardiography / drug effects*
  • Female
  • Fluoroquinolones
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / agonists
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Heart Conduction System
  • Humans
  • Injections, Subcutaneous
  • Liraglutide
  • Male
  • Middle Aged
  • Models, Statistical
  • Moxifloxacin
  • Quinolines / adverse effects
  • Time Factors

Substances

  • Aza Compounds
  • Fluoroquinolones
  • Quinolines
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Moxifloxacin