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.

Liraglutide (Saxenda&lt;sup&gt;&#174;&lt;/sup&gt;) as a Treatment for Obesity

“…A randomized, placebo-controlled, cross-over study, found no clinically relevant prolongation in the QTc interval after daily doses up to 1.8 mg were given [20]. The maximum plasma concentrations (Cmax) in overweight and obese subjects treated with liraglutide 3 mg was similar to the Cmax observed in healthy volunteers.…”

Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2—3 liraglutide clinical development studies

“…While liraglutide and other GLP-1 agonists have shown positive effects on haemoglobin A1c, body weight, and blood pressure in patients with type 2 diabetes, emerging data suggest potential cardioprotective effects and no clinically significant changes in repolarisation patterns, or effects on the QT interval. 15 It should be noted that the cardiovascular safety of liraglutide will be prospectively evaluated in the international LEADER™ trial, which is enrolling 9000 patients with type 2 diabetes and a broad range of cardiovascular risk, including known coronary heart disease. Patients will be randomised 1:1 to liraglutide or placebo and will be followed for up to 5 years for adjudicated macrovascular events including non-fatal MI, stroke, and cardiovascular death.…”

Adverse Effects of GLP-1 Receptor Agonists

“…Exenatide, liraglutide, and albiglutide do not cause any clinically relevant increase in the QTc interval [98][99][100][101]. Exenatide does not prolong QTc even at supratherapeutic concentrations [102].…”