Considerations for assessing the potential effects of antidiabetes drugs on cardiac ventricular repolarization: A report from the Cardiac Safety Research Consortium

Am Heart J. 2015 Jul;170(1):23-35. doi: 10.1016/j.ahj.2015.03.007. Epub 2015 Mar 18.

Abstract

Thorough QT studies conducted according to the International Council on Harmonisation E14 guideline are required for new nonantiarrhythmic drugs to assess the potential to prolong ventricular repolarization. Special considerations may be needed for conducting such studies with antidiabetes drugs as changes in blood glucose and other physiologic parameters affected by antidiabetes drugs may prolong the QT interval and thus confound QT/corrected QT assessments. This review discusses potential mechanisms for QT/corrected QT interval prolongation with antidiabetes drugs and offers practical considerations for assessing antidiabetes drugs in thorough QT studies. This article represents collaborative discussions among key stakeholders from academia, industry, and regulatory agencies participating in the Cardiac Safety Research Consortium. It does not represent regulatory policy.

Publication types

  • Review

MeSH terms

  • Arrhythmias, Cardiac / chemically induced*
  • Brugada Syndrome
  • Cardiac Conduction System Disease
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Electrocardiography
  • Glucagon-Like Peptide-1 Receptor
  • Glycoside Hydrolase Inhibitors
  • Heart Conduction System / abnormalities*
  • Heart Ventricles
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Long QT Syndrome / chemically induced*
  • Patch-Clamp Techniques
  • Receptors, Glucagon / agonists
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sulfonylurea Compounds / adverse effects
  • Thiazolidinediones / adverse effects
  • Ventricular Function

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycoside Hydrolase Inhibitors
  • Hypoglycemic Agents
  • Receptors, Glucagon
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sulfonylurea Compounds
  • Thiazolidinediones