Details
The U.S. Food and Drug Administration (FDA) initiated this study in the Sentinel System to assess the cardiovascular safety of tirzepatide. Results from the placebo-controlled clinical trials for Mounjaro (tirzepatide) reported a dose-related heart rate increase in the tirzepatide-treated subjects, with higher frequencies reported in trials conducted in Japan. The FDA conducted this descriptive analysis in a real-world setting to assess the clinical relevance of the clinical trial findings and inform future Sentinel assessments as needed.
This Sentinel study sought to describe the incidence rate of hospitalized tachyarrhythmia in patients with type 2 diabetes who newly initiated Mounjaro or other long-acting glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Other GLP-1 RAs included in the analysis were: Bydureon (exenatide), Bydureon BCISE (exenatide), Ozempic (semaglutide), Rybelsus (semaglutide), Wegovy (semaglutide), Saxenda (liraglutide), Victoza (liraglutide), Trulicity (dulaglutide), and Xultophy (insulin degludec/liraglutide). Hospitalized tachyarrhythmia was defined as the presence of any of the following conditions: atrial fibrillation and flutter, sinus tachycardia, supraventricular tachycardia, other tachycardia, cardiac arrest, ventricular fibrillation and flutter, and ventricular tachycardia.
The results described the incidence rate of hospitalized tachyarrhythmia by product and patient characteristics, including race subgroups. From May 13, 2022, to June 30, 2023, the study identified 18,842 new users of Mounjaro. Of these, 102 (0.54%) experienced hospitalized tachyarrhythmia, resulting in an incidence rate of 472.43 per 10,000 patient-years. Among the 108 Asian new users of Mounjaro, none experienced an event of hospitalized tachyarrhythmia. Among other GLP-1 RAs, Ozempic had the largest number of new users (N= 117,008), followed by Trulicity (N= 66,978) and Rybelsus (N= 34,058). The incidence rate of hospitalized tachyarrhythmia in the eight GLP-1 RA products was 392.98 per 10,000 patient-years for Bydureon, 488.45 per 10,000 patient-years for Ozempic, 381.28 per 10,000 patient-years for Rybelsus, 199.10 per 10,000 patient-years for Saxenda, 500.90 per 10,000 patient-years for Trulicity, 137.10 per 10,000 patient-years for Wegovy, 601.14 per 10,000 patient-years for Victoza, and 349.71 per 10,000 patient-years for Xultophy.
The results of this Sentinel study contributed to the FDA's discussion regarding the planned pharmacovigilance activities for tirzepatide. Due to the descriptive nature and the short evaluation period, this study did not provide definitive information regarding the cardiovascular safety of tirzepatide. The FDA concluded that an additional Sentinel analysis was not warranted since no safety signals were identified through other pharmacovigilance activities thus far, no major findings emerged from related studies for tirzepatide, and data from the cardiovascular outcomes trial (CVOT) for Mounjaro are anticipated to be available by the end of 2025.