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 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.
Chatterjee
Dhruba J
DJ
Clinical Research, Novo Nordisk, Inc, Princeton, NJ 08540, USA. dcee@novonordisk.com
Khutoryansky
Naum
N
Zdravkovic
Milan
M
Sprenger
Craig R
CR
Litwin
Jeffrey S
JS
D000293:Adolescent; D000328:Adult; D001372:Aza Compounds / Q000009:adverse effects; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D024841:Fluoroquinolones; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000819:agonists / Q000031:analogs & derivatives*; D006329:Heart Conduction System; D006801:Humans; D007279:Injections, Subcutaneous; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D000077266:Moxifloxacin; D011804:Quinolines / Q000009:adverse effects; D013997:Time Factors
D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077266:Moxifloxacin