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

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 recor...

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Published inJournal of clinical pharmacology Vol. 49; no. 11; p. 1353
Main Authors Chatterjee, Dhruba J, Khutoryansky, Naum, Zdravkovic, Milan, Sprenger, Craig R, Litwin, Jeffrey S
Format Journal Article
LanguageEnglish
Published England 01.11.2009
Subjects
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
Quinolines - adverse effects
Time Factors
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Summary: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.
ISSN:1552-4604
DOI:10.1177/0091270009339189