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

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.