1. 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.
- Author
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Chatterjee DJ, Khutoryansky N, Zdravkovic M, Sprenger CR, and Litwin JS
- Subjects
- Adolescent, Adult, Aza Compounds adverse effects, Cross-Over Studies, Diabetes Mellitus, Type 2 drug therapy, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical methods, Female, Fluoroquinolones, Glucagon-Like Peptide 1 administration & dosage, Glucagon-Like Peptide 1 adverse effects, Glucagon-Like Peptide 1 agonists, Heart Conduction System, Humans, Injections, Subcutaneous, Liraglutide, Male, Middle Aged, Models, Statistical, Moxifloxacin, Quinolines adverse effects, Time Factors, Electrocardiography drug effects, Glucagon-Like Peptide 1 analogs & derivatives
- 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.
- Published
- 2009
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