Semaglutide at doses up to 1.5 mg once weekly did not prolong cardiac repolarization in healthy subjects, as the upper limit of the 90% confidence interval for the placebo-subtracted QTcI difference was <10 ms at all time points.
RCT (n=166)
Double-blind
Randomized
No
Does semaglutide prolong the QTc interval in healthy subjects?
Semaglutide at therapeutic and supratherapeutic doses does not prolong the QTc interval in healthy subjects, indicating no increased risk for ventricular arrhythmias.
Mean Difference: -3.2 (95% CI -6.6–0.3)
p-value: p=<0.0001
INTRODUCTION: Semaglutide is a glucagon-like peptide-1 (GLP-1) analog approved for the once-weekly treatment of type 2 diabetes. The objective of this 16-week, double-blind, single-center thorough QT study was to confirm that semaglutide treatment does not prolong cardiac repolarization versus placebo. Prolongation of the QT interval is a biomarker for ventricular tachyarrhythmia. METHODS: . To assess QT assay sensitivity, subjects in the placebo group received a single 400 mg moxifloxacin dose as positive control, and placebo in a crossover fashion. The primary endpoint was the time-matched change from baseline in QT interval corrected individually for heart rate (ΔQTcI), calculated from 11 electrocardiogram recordings from 0 to 48 h after the last 1.5 mg dose. Similar assessments were made for the therapeutic 0.5 and 1.0 mg semaglutide dose levels. RESULTS: No QTcI prolongation occurred with any semaglutide dose; the upper limits of two-sided 90% confidence intervals of the placebo-subtracted ΔQTcI were < 10 ms at all doses and time points. Exposure-response analysis showed no dependence of QTcI on semaglutide concentration. QT assay sensitivity was confirmed. The semaglutide safety profile was similar to that of other GLP-1 receptor agonists. CONCLUSION: Based on investigations of QT/QTc, no concern with regard to ventricular arrhythmias was raised as semaglutide did not prolong the cardiac repolarization duration in healthy subjects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT 02064348. FUNDING: Novo Nordisk.
Demmel et al. (Thu,) conducted a rct in Healthy subjects (n=166). Semaglutide vs. Placebo was evaluated on Time-matched change from baseline in QT interval corrected individually for heart rate (ΔQTcI) from 0 to 48 h after the last 1.5 mg dose (MD -3.2 ms, 95% CI -6.6 to 0.3, p=<0.0001). Semaglutide at doses up to 1.5 mg once weekly did not prolong cardiac repolarization in healthy subjects, as the upper limit of the 90% confidence interval for the placebo-subtracted QTcI difference was <10 ms at all time points.